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Biol."},{"key":"10.1016\/j.bioorg.2026.109775_bb0395","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.chembiol.2022.09.004","article-title":"Acute pharmacological degradation of ERK5 does not inhibit cellular immune response or proliferation","volume":"29","author":"You","year":"2022","journal-title":"cell Chem. 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