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Rab35 is a small GTPase that is involved in many cellular processes, including membrane trafficking, cell polarity, lipid homeostasis, immunity, phagocytosis and cytokinesis. Recent studies showed that activating mutations confer Rab35 with oncogenic properties. Conversely, downregulation of Rab35 inverts apico‐basal cell polarity and promotes cell migration. Here we review Rab35’s known functions in membrane trafficking and signaling, cell division and cell migration in cancer cells and discuss the importance of Rab35‐dependent membrane trafficking in cancer progression. 相似文献
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Distribution of amiloride-sensitive sodium channels in the oral cavity of the hamster 总被引:3,自引:3,他引:0
The distribution of amiloride-sensitive sodium channels (ASSCs) in taste
buds isolated from the oral cavity of hamsters was assessed by patch clamp
recording. In contrast to the case for rats, taste cells from the
fungiform, foliate and vallate papillae and from the soft palate all
contain functional ASSCs. The differential distribution of ASSCs between
the hamster and the rat may be important for understanding the physiology
underlying the differing behavioral responses of these species to sodium
salts.
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Lippa B Pan G Corbett M Li C Kauffman GS Pandit J Robinson S Wei L Kozina E Marr ES Borzillo G Knauth E Barbacci-Tobin EG Vincent P Troutman M Baker D Rajamohan F Kakar S Clark T Morris J 《Bioorganic & medicinal chemistry letters》2008,18(11):3359-3363
Based on a high throughput screening hit, pyrrolopyrimidine inhibitors of the Akt kinase are explored. X-ray co-crystal structures of two lead series results in the understanding of key binding interactions, the design of new lead series, and enhanced potency. The syntheses of these series and their biological activities are described. Spiroindoline 13j is found to have an Akt1 kinase IC(50) of 2.4+/-0.6 nM, Akt cell potency of 50+/-19 nM, and provides 68% inhibition of tumor growth in a mouse xenograft model (50 mg/kg, qd, po). 相似文献
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Antane S Caufield CE Hu W Keeney D Labthavikul P Morris K Naughton SM Petersen PJ Rasmussen BA Singh G Yang Y 《Bioorganic & medicinal chemistry letters》2006,16(1):176-180
Pulvinones were synthesized (>180) in arrays and evaluated as inhibitors of early stage cell wall biosynthesis enzymes MurA-MurD. Several pulvinones inhibited Mur enzymes with IC(50)'s in the 1-10 microg/mL range and demonstrated antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphyloccus aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae. 相似文献
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Beernink PT Shaughnessy J Braga EM Liu Q Rice PA Ram S Granoff DM 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(6):3606-3614
Certain pathogens recruit host complement inhibitors such as factor H (fH) to evade the immune system. Microbial complement inhibitor-binding molecules can be promising vaccine targets by eliciting Abs that neutralize this microbial defense mechanism. One such Ag, meningococcal factor H-binding protein (fHbp), was used in clinical trials before the protein was discovered to bind fH. The potential effect of fH binding on vaccine immunogenicity had not been assessed in experimental animals because fHbp binds human fH specifically. In this study, we developed a human fH transgenic mouse model. Transgenic mice immunized with fHbp vaccine had 4- to 8-fold lower serum bactericidal Ab responses than those of control mice whose native fH did not bind the vaccine. In contrast, Ab responses were unimpaired in transgenic mice immunized with a control meningococcal group C polysaccharide-protein conjugate vaccine. In transgenic mice, immunization with an fH nonbinding mutant of fHbp elicited Abs with higher bactericidal activity than that of fHbp vaccination itself. Abs elicited by the mutant fHbp more effectively blocked fH binding to wild-type fHbp than Abs elicited by fHbp that bound fH. Thus, a mutant fHbp vaccine that does not bind fH but that retains immunogenicity is predicted to be superior in humans to an fHbp vaccine that binds human fH. In the case of mutant fHbp vaccination, the resultant Ab responses may be directed more at epitopes in or near the fH binding site, which result in greater complement-mediated serum bactericidal activity; these epitopes may be obscured when human fH is bound to the wild-type fHbp vaccine. 相似文献