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|
||
<a href="/clipboard/"
|
||
class="search-input-link clipboard-link hidden"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="clipboard">
|
||
Clipboard <span class="amount-in-clipboard"></span>
|
||
</a>
|
||
</div>
|
||
|
||
<span class="search-input-link user-guide-link" role="navigation" aria-label="User guide">
|
||
<a href="/help/"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F19401591%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F19401591%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="gQcE0YtXL4QXMcd7UBSi67AaQ8QAYZIXxDWJDOWjlFDrGDjXxUvkAf6OocyMRAgh">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="gQcE0YtXL4QXMcd7UBSi67AaQ8QAYZIXxDWJDOWjlFDrGDjXxUvkAf6OocyMRAgh">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="gQcE0YtXL4QXMcd7UBSi67AaQ8QAYZIXxDWJDOWjlFDrGDjXxUvkAf6OocyMRAgh">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 19401591 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 19401591"/>
|
||
<input type="hidden" name="email-subject-hash" value="cc46889a224e78eb71b5cec7235edc3c990422a36e3d424f65567b34cd6717e7"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="gQcE0YtXL4QXMcd7UBSi67AaQ8QAYZIXxDWJDOWjlFDrGDjXxUvkAf6OocyMRAgh">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="gQcE0YtXL4QXMcd7UBSi67AaQ8QAYZIXxDWJDOWjlFDrGDjXxUvkAf6OocyMRAgh">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="gQcE0YtXL4QXMcd7UBSi67AaQ8QAYZIXxDWJDOWjlFDrGDjXxUvkAf6OocyMRAgh">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="gQcE0YtXL4QXMcd7UBSi67AaQ8QAYZIXxDWJDOWjlFDrGDjXxUvkAf6OocyMRAgh">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="gQcE0YtXL4QXMcd7UBSi67AaQ8QAYZIXxDWJDOWjlFDrGDjXxUvkAf6OocyMRAgh">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="19401591">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https:///www.science.org/doi/10.1126/scisignal.2000118?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub 0pubmed"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=4487&itool=Abstract-def&log$=linkouticon&uid=19401591&db=pubmed&nlmid=101465400"
|
||
title="See full text options at Atypon"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Atypon"
|
||
data-ga-label="19401591"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.science.org-pb-assets-images-logos-pubmed-signaling.gif" alt="Atypon full text link"><span class="text">
|
||
|
||
Atypon
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/19401591/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=19401591&db=pubmed&nlmid=101465400"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="19401591"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/19401591/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/19401591/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="19401591" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F19401591%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="gQcE0YtXL4QXMcd7UBSi67AaQ8QAYZIXxDWJDOWjlFDrGDjXxUvkAf6OocyMRAgh"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
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Galpha(i1) and Galpha(i3) are required for epidermal growth factor-mediated activation of the Akt-mTORC1 pathway
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Galpha(i1) and Galpha(i3) are required for epidermal growth factor-mediated activation of the Akt-mTORC1 pathway
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The precise mechanism whereby epidermal growth factor (EGF) activates the serine-threonine kinase Akt and the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) remains elusive. Here, we report that the alpha subunits of the heterotrimeric guanine nucleotide-binding proteins (G proteins) Galpha(i1) and Galpha(i3) are critical for this activation process. Both Galpha(i1) and Galpha(i3) formed complexes with growth factor receptor binding 2 (Grb2)-associated binding protein 1 (Gab1) and the EGF receptor (EGFR) and were required for the phosphorylation of Gab1 and its subsequent interaction with the p85 subunit of phosphatidylinositol 3-kinase in response to EGF. Loss of Galpha(i1) and Galpha(i3) severely impaired the activation of Akt and of p70 S6 kinase and 4E-BP1, downstream targets of mTORC1, in response to EGF, heparin-binding EGF-like growth factor, and transforming growth factor alpha, but not insulin, insulin-like growth factor, or platelet-derived growth factor. In addition, ablation of Galpha(i1) and Galpha(i3) largely inhibited EGF-induced cell growth, migration, and survival and the accumulation of cyclin D1. Overall, this study suggests that Galpha(i1) and Galpha(i3) lie downstream of EGFR, but upstream of Gab1-mediated activation of Akt and mTORC1, thus revealing a role for Galpha(i) proteins in mediating EGFR signaling.
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<div class="figure-caption-contents"><p> Gα <sub> i1 </sub> and Gα <sub> i3… </sub> </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 1 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Gα <sub> i1 </sub> and Gα <sub> i3 </sub> are required for the activation of Akt and… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
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|
||
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
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||
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|
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|
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<strong class="figure-label">
|
||
Fig. 1
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Gα<sub>i1</sub> and Gα<sub>i3</sub> are required for the activation of Akt and mTORC1 by EGF. WT and Gα<sub>i1</sub>, Gα<sub>i3</sub> DKO MEFs were treated with different doses of EGF for 15 min (<b>A</b>) or with EGF (100 ng/ml) for the indicated times (<b>B</b>). Gα<sub>i1</sub>, Gα<sub>i3</sub>, pEGFR(1173Y), pAkt(473S), pAkt(308T), pGSK-3β(9S), pFoxo3(32T), pp70S6K(389T), pS6 (235/236S), p4E-BP1(65S), Akt1–2, S6, and EGFR were detected by Western blotting analysis. (<b>C</b>) WT, Gα<sub>i1</sub>-deficient, Gα<sub>i3</sub>-deficient, or DKO MEFs were treated with EGF (100 ng/ml) for the indicated times. Gα<sub>i3</sub>, pAkt(473S), pS6(235/236S), p4E-BP1(65S), and Akt1–2 were detected by Western blotting analysis. (<b>D</b>) WT and Gα<sub>i2</sub>-deficient MEFs were treated with EGF (100 ng/ml) for the indicated times. Gα<sub>i2</sub>, pAkt(473S), pS6K(389T), p4E-BP1(65S), and AKT1–2 were detected by Western blotting analysis. The experiments were repeated at least three times and similar results were obtained in each case.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="1"
|
||
data-label-slug="fig-2">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba51/4138699/a13b11c28f90/nihms460513f2.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-1"
|
||
role="button"
|
||
data-image-width="800"
|
||
data-image-height="503"
|
||
data-image-alt="Fig. 2"
|
||
data-pmc-id="PMC4138699"
|
||
data-figure-id="F2">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-1"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba51/4138699/698d57acdafd/nihms460513f2.gif"
|
||
alt="Fig. 2" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="800">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="503">
|
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|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
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<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 2 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Loss of Gα <sub> i1 </sub> and… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 2 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Loss of Gα <sub> i1 </sub> and Gα <sub> i3 </sub> severely impairs activation of Akt and… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Fig. 2
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Loss of Gα<sub>i1</sub> and Gα<sub>i3</sub> severely impairs activation of Akt and mTORC1 by HB-EGF and TGF-α, but not by insulin, IGF, or PDGF. WT and DKO MEFs were treated with TGF-α (100 ng/ml), HB-EGF (100 ng/ml), PDGF-BB (25 ng/ml) (<b>A</b>), or with insulin (1 μg/ml) or IGF-1 (10 ng/ml) (<b>B</b>) for the indicated times. Gα<sub>i3</sub>, pAkt(308T), pAkt(473S), pGSK-3β(9/21S), pS6K(389T), pS6(235/236S), p4E-BP1(65S), Akt1–2, and β-actin were detected by Western blotting analysis. (<b>C</b>) EGF-or insulin-induced pSTAT5(694Y) and Akt(473S) in WT and DKO MEFs were detected by Western blotting analysis. (<b>D</b>) EGF-induced phosphorylation of PLC-γ(783Y) and Akt(473S) were determined by Western blotting. The experiments were repeated at least three times and similar results were obtained in each case.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="2"
|
||
data-label-slug="fig-3">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba51/4138699/fa0edc92186d/nihms460513f3.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-2"
|
||
role="button"
|
||
data-image-width="800"
|
||
data-image-height="555"
|
||
data-image-alt="Fig. 3"
|
||
data-pmc-id="PMC4138699"
|
||
data-figure-id="F3">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-2"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba51/4138699/01f57827b36c/nihms460513f3.gif"
|
||
alt="Fig. 3" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="800">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="555">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 3 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Gα <sub> i1 </sub> and Gα <sub> i3… </sub> </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 3 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Gα <sub> i1 </sub> and Gα <sub> i3 </sub> proteins are critical for the phosphorylation of Akt473S… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Fig. 3
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Gα<sub>i1</sub> and Gα<sub>i3</sub> proteins are critical for the phosphorylation of Akt473S and 4E-BP1(65S) in response to EGF. (<b>A</b>) Knockdown of Gα<sub>i1</sub> and Gα<sub>i3</sub> decreases the activation of Akt by EGF, but not insulin. WT MEFs transfected with siRNA oligos specific for Gα<sub>i1</sub> and Gα<sub>i3</sub> and DKO MEFs were treated with EGF (100 ng/ml) or insulin (1 μg/ml) for the indicated times. pAkt(308T), pAkt(473S), pGSK-3β(S9), Akt1–2, β-actin, Gα<sub>i1</sub>, and Gα<sub>i3</sub> were detected by Western blotting. (<b>B</b>) Exogenous Gα<sub>i1</sub> and Gα<sub>i3</sub> rescue the activation of Akt and 4E-BP1 in DKO MEFs in response to EGF. DKO MEFs were transfected with vectors encoding WT Gα<sub>i1</sub> or Gα<sub>i3</sub> (4 μg). Cells were treated with EGF (100 ng/ml) for the indicated times. pAkt(308T), pAkt(473S), S6K(389T), S6(235/236S), β-actin, Gα<sub>i1</sub>, and Gα<sub>i3</sub> were detected by Western blotting analysis. (<b>C</b>) Cotransfection of DN mutants of Gα<sub>i1</sub> and Gα<sub>i3</sub> inhibits the activation of Akt by EGF. WT MEFs were cotransfected with DN, EE-tagged Gα<sub>i1</sub> and Gα<sub>i3</sub> expression vectors (2 μg each) or were untransfected as controls followed by treatment with EGF (100 ng/ml) for the indicated times. pAkt(473S), pGSK-3β(9S), pS6K(389T), Akt1–2, EE tag, and Gα<sub>i3</sub> were detected by Western blotting. (<b>D</b>) Constitutively active (CA) Gα<sub>i3</sub>(Q204L) induces the phosphorylation of Akt(473S) and S6(235/236S). DKO cells were transfected with a vector expressing Gα<sub>i3</sub>(Q204L). pAkt(473S), pS6(235/236S), Gα<sub>i3</sub>, and β-actin were determined by Western blotting analysis. (<b>E</b>) WT MEFs were pretreated overnight with pertussis toxin (PTX, 100 ng/ml) followed by treatment with EGF. pAkt(473S), pGSK-3β(9S), p4E-BP1(65S), pS6K(389T), and β-actin were detected by Western blotting. All transfection experiments were repeated at least twice and similar results were obtained in each case.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="3"
|
||
data-label-slug="fig-4">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba51/4138699/9e56748165c5/nihms460513f4.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-3"
|
||
role="button"
|
||
data-image-width="726"
|
||
data-image-height="460"
|
||
data-image-alt="Fig. 4"
|
||
data-pmc-id="PMC4138699"
|
||
data-figure-id="F4">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-3"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba51/4138699/dc839a20311e/nihms460513f4.gif"
|
||
alt="Fig. 4" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="726">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="460">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 4 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> EGF-induced phosphorylation of Gab1 depends… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 4 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> EGF-induced phosphorylation of Gab1 depends on Gα <sub> i1 </sub> and Gα <sub> i3 </sub> . (… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Fig. 4
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">EGF-induced phosphorylation of Gab1 depends on Gα<sub>i1</sub> and Gα<sub>i3</sub>. (<b>A</b>) Gab1 is required for the activation of Akt by EGF and TGF-α, but not by insulin, IGF, and PDGF. pAkt(308T) and pAkt(473S) were detected in WT and Gab1-deficient MEFs treated with EGF (100 ng/ml), TGF-α (100 ng/ml), PDGF-BB (25 ng/ml), insulin (1 μg/ml), or IGF-1 (10 ng/ml). (<b>B</b>) Gα<sub>i1</sub> and Gα<sub>i3</sub> are required for the phosphorylation of Gab1 in response to EGF. pGab1(307Y) and pGab1(627Y) in WT and DKO MEFs treated with EGF (100 ng/ml) were detected by Western blotting analysis. (<b>C</b>) Loss of Gα<sub>i1</sub> and Gα<sub>i3</sub> largely impairs phosphorylation of Akt and Gab1 in response to EGF and TGF-α, but not insulin. WT and DKO MEFs were treated with EGF (100 ng/ml), insulin (1 μg/ml), or TGF-α (100 ng/ml) for 5 min. pAkt(308T), pAkt(473S), pGab1(627Y), Gab1, PI3Kp85, and ERK1–2 were detected by Western blotting analysis.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="4"
|
||
data-label-slug="fig-5">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba51/4138699/f0cc713615fb/nihms460513f5.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-4"
|
||
role="button"
|
||
data-image-width="762"
|
||
data-image-height="557"
|
||
data-image-alt="Fig. 5"
|
||
data-pmc-id="PMC4138699"
|
||
data-figure-id="F5">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-4"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba51/4138699/49d2ec29bc11/nihms460513f5.gif"
|
||
alt="Fig. 5" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="762">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="557">
|
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|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 5 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> EGF induces the association of… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 5 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> EGF induces the association of Gab1 with Gα <sub> i1 </sub> and Gα <sub> i3 </sub> ,… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Fig. 5
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">EGF induces the association of Gab1 with Gα<sub>i1</sub> and Gα<sub>i3</sub>, and the EGF-induced interaction of Gab1 with PI3K p85 depends on Gα<sub>i1</sub> and Gα<sub>i3</sub>. (<b>A</b>) EGF induces the association of Gα<sub>i3</sub> with Gab1. WT and DKO MEFs were treated with EGF (100 ng/ml) for the indicated times and were then lysed. The precleared cell lysates (0.6 mg) were incubated with anti-EGFR or anti-Gα<sub>i3</sub> antibodies overnight at 4°C, followed by incubation with protein A/G beads for another 2 hours at 4°C. Beads were washed, boiled, resolved by 10% SDS-PAGE, and proteins were transferred onto a PVDF membrane followed by Western blotting analysis with anti-EGFR, anti-Gα<sub>i3</sub>, and anti-Gab1, respectively. (<b>B</b> and <b>C</b>) EGF induces the association of Gab1 with Gα<sub>i1</sub> and Gα<sub>i3</sub>. WT and DKO MEFs were treated with EGF (100 ng/ml) for the indicated times. The precleared 600-μg aliquots of cell lysates were incubated with anti-Gab1 (<b>B</b>), or with anti-Gab1 and anti-Gα<sub>i1</sub> (<b>C</b>), respectively, followed by Western blotting analysis with anti-Gab1, anti-pGab1(627Y), anti-Gα<sub>i1</sub>, and anti-Gα<sub>i3</sub>, respectively. (<b>D</b>) HEK 293 cells were treated with EGF for 5 min and then lysed. The precleared, 700-μg cell lysates were incubated with anti-EGFR, anti-Gab1, or anti-Gα<sub>i3</sub> and 20 μl of protein A/G beads at 4°C overnight. Beads were washed four times with lysis buffer, boiled, resolved by SDS-PAGE, and transferred onto a PVDF membrane, followed by Western blotting analysis to detect EGFR, Gα<sub>i3</sub>, and Gab1. (<b>E</b>) The same cell lysates used for Fig. 4C were precleared and incubated overnight with anti-p85 and 20 μl of protein A/G beads at 4°C. Beads were washed four times with lysis buffer, boiled, loaded onto an SDS-PAGE gel and transferred onto a PVDF membrane followed by Western blotting analysis to detect Gab1, pGab1(627Y), and PI3K p85. All experiments were repeated at least two or three times and similar results were obtained in each case.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
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|
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data-slide-index="5"
|
||
data-label-slug="fig-6">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba51/4138699/2de346d1a3d8/nihms460513f6.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-5"
|
||
role="button"
|
||
data-image-width="800"
|
||
data-image-height="861"
|
||
data-image-alt="Fig. 6"
|
||
data-pmc-id="PMC4138699"
|
||
data-figure-id="F6">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-5"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba51/4138699/b1dbe01e67f7/nihms460513f6.gif"
|
||
alt="Fig. 6" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="800">
|
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<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="861">
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<p> Fig. 6 </p>
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</strong>
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<div class="figure-caption-contents"><p> Roles for Gα <sub> i1 </sub> and… </p></div>
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<p> Fig. 6 </p>
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<div class="figure-caption-contents"><p> Roles for Gα <sub> i1 </sub> and Gα <sub> i3 </sub> proteins in EGF-mediated cell proliferation, growth,… </p></div>
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Fig. 6
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<div class="figure-caption-contents">Roles for Gα<sub>i1</sub> and Gα<sub>i3</sub> proteins in EGF-mediated cell proliferation, growth, migration, survival, and the production of cyclin D1. (<b>A</b>) Gα<sub>i1</sub> and Gα<sub>i3</sub> are important for EGF-induced cell proliferation. WT and DKO MEFs were treated with EGF (100 ng/ml) for 24 hours. Cell proliferation was determined by the MTT assay. (<b>B</b>) Gα<sub>i1</sub> and Gα<sub>i3</sub> are involved in FBS-induced cell growth. FBS-induced cell growth in both WT and DKO cells was determined by counting cell numbers under a microscope. (<b>C</b>) WT and DKO MEFs were treated with EGF (100 ng/ml) for 4, 8, or 24 hours. The abundance of cyclin D1 was determined by Western blotting analysis with an antibody to cyclin D1. (<b>D</b> and <b>E</b>) Gα<sub>i1</sub> and Gα<sub>i3</sub> are required for EGF-induced cell migration. WT and DKO MEFs were incubated with serum-free medium in the presence or absence of EGF (100 ng/ml) or 10% FBS for 36 hours. In vitro cell migration was determined by the phagokinetic track motility assay (<b>D</b>) or the scratch assay (<b>E</b>). The image represents a minimum of 10 random fields for each group. Magnification: 200× for phagokinetic track motility assay and 100× for scratch assay. (<b>F</b>) Gα<sub>i</sub> proteins are required for EGF-induced cell survival. WT and DKO MEFs were treated with different doses of H<sub>2</sub>O<sub>2</sub> in the presence or absence of EGF (100 ng/ml). After 24 hours, cell viability was measured by the MTT assay. Mitomycin C (10 μg/ml) was always present in the media to prevent cell proliferation from occurring. The data represent the mean ± SE of at least triplicate experiments. *<i>P</i> < 0.05 versus WT groups.</div>
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<p> Fig. 7 </p>
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<div class="figure-caption-contents"><p> Model of Gα <sub> i </sub> -mediated… </p></div>
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<p> Fig. 7 </p>
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<div class="figure-caption-contents"><p> Model of Gα <sub> i </sub> -mediated activation of the PI3K-Akt-mTORC1 pathway in response to… </p></div>
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Fig. 7
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<div class="figure-caption-contents">Model of Gα<sub>i</sub>-mediated activation of the PI3K-Akt-mTORC1 pathway in response to EGF. EGF induces formation of a complex between EGFR, Gα<sub>i</sub>, and Gab1. Recruitment of Gα<sub>i</sub> to the receptor may occur directly or through an as yet unidentified protein. Subsequently, Gα<sub>i</sub> interacts with Gab1, which promotes its phosphorylation by the EGFR or a non-RTK. Activated Gab1 interacts with the regulatory subunit of PI3K (p85), which leads to the activation of the catalytic subunits of PI3K (p110). Active PI3K phosphorylates PIP<sub>2</sub> (phosphatidylinositol 4,5-bisphosphate) to generate PIP<sub>3</sub> (phosphatidylinositol 3,4,5-trisphosphate), which in turn interacts with the pleckstrin homology domain of Akt and PDK1, and PDK1 phosphorylates Akt on Thr<sup>308</sup>. Activated Gab1 uses an unidentified mechanism to trigger the activation of mTORC2, which leads to the phosphorylation of Akt on Ser<sup>473</sup>. When Akt is activated, it phosphorylates FOXO, GSK-3α, and GSK-3β and triggers the activation of mTORC1, which results in phosphorylation of 4E-BP1 and S6K, which in turn phosphorylates S6.</div>
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Rozengurt E. Mitogenic signaling pathways induced by G protein-coupled receptors. J Cell Physiol. 2007;213:589–602.
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Steelman LS, Abrams SL, Whelan J, Bertrand FE, Ludwig DE, Bäsecke J, Libra M, Stivala F, Milella M, Tafuri A, Lunghi P, Bonati A, Martelli AM, McCubrey JA. Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia. Leukemia. 2008;22:686–707.
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Cell Line"
|
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-3"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Cell Line
|
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</button><div id="keyword-actions-mesh-terms-3"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Cell Line"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Cell+Line%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Cell+Line%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Cell Line"[MeSH]"
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data-ga-action="mesh_term"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Line"
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data-ga-category="search_mesh"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Cell Line"[MeSH]"
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data-ga-label=""Cell Line"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Cell Movement / drug effects"
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-4"
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aria-expanded="false"
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data-pinger-ignore>
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Cell Movement / drug effects
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</button><div id="keyword-actions-mesh-terms-4"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Cell Movement / drug effects"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Cell+Movement%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Cell+Movement%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Cell Movement/drug effects"[MeSH]"
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data-ga-action="mesh_term"
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data-ga-label="Cell Movement / drug effects">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Movement"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Cell Movement/drug effects"[MeSH]"
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data-ga-action="add_to_search"
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data-ga-label=""Cell Movement/drug effects"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Cell Proliferation / drug effects"
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-5"
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aria-expanded="false"
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data-pinger-ignore>
|
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Cell Proliferation / drug effects
|
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</button><div id="keyword-actions-mesh-terms-5"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Cell Proliferation / drug effects"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Cell+Proliferation%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Cell+Proliferation%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Cell Proliferation/drug effects"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Proliferation"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Cell Proliferation/drug effects"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Cell Proliferation/drug effects"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Cell Survival / drug effects"
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
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Cell Survival / drug effects
|
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</button><div id="keyword-actions-mesh-terms-6"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Cell Survival / drug effects"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Cell+Survival%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Cell+Survival%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Cell Survival/drug effects"[MeSH]"
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data-ga-action="mesh_term"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Survival"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Cell Survival/drug effects"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Cell Survival/drug effects"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Cells, Cultured"
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
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Cells, Cultured
|
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</button><div id="keyword-actions-mesh-terms-7"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Cells, Cultured"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Cells%2C+Cultured%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Cells%2C+Cultured%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Cells, Cultured"[MeSH]"
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Search in PubMed
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Cells, Cultured"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Cells, Cultured"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Cyclin D"
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-8"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Cyclin D
|
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</button><div id="keyword-actions-mesh-terms-8"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Cyclin D"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Cyclin+D%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Cyclin+D%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Cyclin D"[MeSH]"
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Search in PubMed
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Cyclin+D"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Cyclin D"[MeSH]"
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data-ga-label=""Cyclin D"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Cyclins / metabolism"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-9"
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aria-expanded="false"
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data-pinger-ignore>
|
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Cyclins / metabolism
|
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</button><div id="keyword-actions-mesh-terms-9"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Cyclins / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Cyclins%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Cyclins%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Cyclins/metabolism"[MeSH]"
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Search in PubMed
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Cyclins"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Cyclins/metabolism"[MeSH]"
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data-ga-label=""Cyclins/metabolism"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
|
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aria-label="Toggle dropdown menu for keyword Epidermal Growth Factor / pharmacology*"
|
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-major-10"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Epidermal Growth Factor / pharmacology*
|
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</button><div id="keyword-actions-mesh-terms-major-10"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Epidermal Growth Factor / pharmacology*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Epidermal+Growth+Factor%2Fpharmacology%22%5BMAJR%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Epidermal+Growth+Factor%2Fpharmacology%22%5BMAJR%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Epidermal Growth Factor/pharmacology"[MAJR]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Epidermal+Growth+Factor"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Epidermal Growth Factor/pharmacology"[MAJR]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword ErbB Receptors / metabolism"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-11"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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ErbB Receptors / metabolism
|
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</button><div id="keyword-actions-mesh-terms-11"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword ErbB Receptors / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22ErbB+Receptors%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22ErbB+Receptors%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="ErbB Receptors/metabolism"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""ErbB Receptors/metabolism"[MeSH]"
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data-ga-category="search"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Fibroblasts / cytology"
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-12"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Fibroblasts / cytology
|
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</button><div id="keyword-actions-mesh-terms-12"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Fibroblasts / cytology"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Fibroblasts%2Fcytology%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Fibroblasts%2Fcytology%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Fibroblasts/cytology"[MeSH]"
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Search in PubMed
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Fibroblasts/cytology"[MeSH]"
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data-ga-category="search"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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tabindex="0"
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data-pinger-ignore>
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Fibroblasts / drug effects
|
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</button><div id="keyword-actions-mesh-terms-13"
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class="keyword-actions-dropdown dropdown dropdown-container"
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aria-label="Dropdown menu for keyword Fibroblasts / drug effects"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Fibroblasts%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Fibroblasts%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Phosphatidylinositol+3-Kinases"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Phosphoproteins / metabolism
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Phosphorylation / drug effects
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Protein Binding
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Protein Isoforms / metabolism
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Add to Search
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Proteins
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aria-label="Dropdown menu for keyword Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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Proto-Oncogene Proteins c-akt / metabolism*
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Signal Transduction / drug effects*
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Transcription Factors / metabolism*
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</div>
|
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|
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|
||
|
||
<div id="substances" class="substances keywords-section">
|
||
<h2 class="title">
|
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Substances
|
||
</h2>
|
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|
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<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Adaptor Proteins, Signal Transducing"
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Adaptor Proteins, Signal Transducing
|
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hidden
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aria-label="Dropdown menu for keyword Adaptor Proteins, Signal Transducing"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Adaptor+Proteins%2C+Signal+Transducing%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Adaptor+Proteins%2C+Signal+Transducing%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Adaptor Proteins, Signal Transducing"[nm]"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Cyclin D"
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aria-expanded="false"
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Cyclin D
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</button><div id="keyword-actions-substances-1"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Cyclin D"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Cyclin+D%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Cyclin+D%22%5Bnm%5D&sort=date&sort_order=desc"
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aria-expanded="false"
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Cyclins
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</button><div id="keyword-actions-substances-2"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Cyclins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Cyclins%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Cyclins%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Cyclins"[nm]"
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Search in PubMed
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Search in MeSH
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data-search-term=""Cyclins"[nm]"
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data-ga-label=""Cyclins"[nm]"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Gab1 protein, mouse"
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Gab1 protein, mouse
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</button><div id="keyword-actions-substances-3"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Gab1 protein, mouse"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Gab1+protein%2C+mouse%22%5Bnm%5D&sort=date&sort_order=desc"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Multiprotein Complexes"
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Multiprotein Complexes
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aria-label="Dropdown menu for keyword Multiprotein Complexes"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Phosphoproteins"
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tabindex="0"
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aria-expanded="false"
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Phosphoproteins
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</button><div id="keyword-actions-substances-5"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Phosphoproteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Phosphoproteins%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Phosphoproteins%22%5Bnm%5D&sort=date&sort_order=desc"
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Search in PubMed
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Search in MeSH
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Protein Isoforms"
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tabindex="0"
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aria-controls="keyword-actions-substances-6"
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aria-expanded="false"
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data-pinger-ignore>
|
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Protein Isoforms
|
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</button><div id="keyword-actions-substances-6"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Protein Isoforms"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Protein+Isoforms%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Protein+Isoforms%22%5Bnm%5D&sort=date&sort_order=desc"
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Search in PubMed
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Protein Isoforms"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Protein Isoforms"[nm]"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Proteins"
|
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tabindex="0"
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aria-controls="keyword-actions-substances-7"
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aria-expanded="false"
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data-pinger-ignore>
|
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Proteins
|
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</button><div id="keyword-actions-substances-7"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Proteins"[nm]"
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Search in PubMed
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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role="button"
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data-search-term=""Proteins"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Proteins"[nm]"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Transcription Factors"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-8"
|
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aria-expanded="false"
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data-pinger-ignore>
|
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Transcription Factors
|
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</button><div id="keyword-actions-substances-8"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Transcription Factors"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Transcription+Factors%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Transcription+Factors%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Transcription Factors"[nm]"
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data-ga-action="substance"
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Search in PubMed
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Search in MeSH
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ref="linksrc=add_to_search_link"
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role="button"
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data-search-term=""Transcription Factors"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Transcription Factors"[nm]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Epidermal Growth Factor"
|
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
|
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Epidermal Growth Factor
|
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</button><div id="keyword-actions-substances-9"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Epidermal Growth Factor"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Epidermal+Growth+Factor%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Epidermal+Growth+Factor%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Epidermal Growth Factor"[nm]"
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Search in PubMed
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Epidermal Growth Factor"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Epidermal Growth Factor"[nm]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword ErbB Receptors"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-10"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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ErbB Receptors
|
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</button><div id="keyword-actions-substances-10"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword ErbB Receptors"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22ErbB+Receptors%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22ErbB+Receptors%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="ErbB Receptors"[nm]"
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data-ga-action="substance"
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