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Sabina C Cosulich Vivienne Worrall Philip J Hedge Stephen Green Paul R ClarkeAuthor vitae 《Current biology : CB》1997,7(12):913
Background: The Bcl-2 family of proteins plays a key role in the regulation of apoptosis. Some family members prevent apoptosis induced by a variety of stimuli, whereas others promote apoptosis. Competitive dimerisation between family members is thought to regulate their function. Homologous domains within individual proteins are necessary for interactions with other family members and for activity, although the specific mechanisms might differ between the pro-apoptotic and anti-apoptotic proteins.Results: Using a cell-free system based on extracts of Xenopus eggs, we have investigated the role of the Bcl-2 homology domain 3 (BH3) from different members of the Bcl-2 family. BH3 domains from the pro-apoptotic proteins Bax and Bak, but not the BH3 domain of the anti-apoptotic protein Bcl-2, induced apoptosis in this system, as determined by the rapid activation of specific apoptotic proteases (caspases) and by DNA fragmentation. The apoptosis-inducing activity of the BH3 domains requires both membrane and cytosolic fractions of cytoplasm, involves the release of cytochrome c from mitochondria and is antagonistic to Bcl-2 function. Short peptides, corresponding to the minimal sequence of BH3 domains required to bind anti-apoptotic Bcl-2 family proteins, also trigger apoptosis in this system.Conclusions: The BH3 domains of pro-apoptotic proteins are sufficient to trigger cytochrome c release, caspase activation and apoptosis. These results support a model in which pro-apoptotic proteins, such as Bax and Bak, bind to Bcl-2 via their BH3 domains, inactivating the normal ability of Bcl-2 to suppress apoptosis. The ability of synthetic peptides to reproduce the effect of pro-apoptotic BH3 domains suggests that such peptides may provide the basis for engineering reagents to control the initiation of apoptosis. 相似文献
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TDP‐43 loss of function inhibits endosomal trafficking and alters trophic signaling in neurons
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Benjamin M Schwenk Hannelore Hartmann Alperen Serdaroglu Martin H Schludi Daniel Hornburg Felix Meissner Denise Orozco Alessio Colombo Sabina Tahirovic Meike Michaelsen Franziska Schreiber Simone Haupt Michael Peitz Oliver Brüstle Clemens Küpper Thomas Klopstock Markus Otto Albert C Ludolph Thomas Arzberger Peer‐Hendrik Kuhn Dieter Edbauer 《The EMBO journal》2016,35(21):2350-2370
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Previous work has shown that the components (phosphorylated phosphatinositols) and enzyme activities (phosphatidylinositol kinase and diacylglycerol kinase) of the phosphatidylinositol (PI) cycle are present in suspension cultured Catharanthus roseus cells. The phospholipid kinase activities can be determined in situ by phosphorylation with labeled exogenous ATP. Incorporation of 32P into phosphorylated PI and phosphatidic acid, the products of PI kinase and diacylglycerol kinase, is reduced in the presence of low cytokinin concentrations; the concentrations for 50% inhibition are in the range 1 μM. The molecular targets of this phytohormone action are discussed. 相似文献
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M. Hergersberg Jaya Balakrishnan Thomas Bettecken Francoise Chevalier-Porst Christian Brägger René Burger Inge Einschenk Sabina Liechti-Gallati Michael Morris Daniel Schorderet Francine Thonney Hans Moser Naseem Malik 《Human genetics》1997,100(2):220-223
We have analysed 1173 cystic fibrosis (CF) chromosomes from Switzerland for eight mutations in the CF transmembrane conductance
regulator (CFTR) gene. This permitted the identification of 88.5% of all mutations present. A novel insertion mutation in
exon 20 of the CFTR gene, 3905insT, was discovered. This mutation accounted for 4.8% of CFTR gene mutations in Switzerland
and has since been identified in other populations of probable Swiss descent. It is associated with a highly variable clinical
phenotype but always with pancreatic insufficiency. Haplotype analysis with three intragenic microsatellites in the CFTR gene
showed that the mutation is associated with a haplotype rarely identified on other CFTR alleles and, therefore, that the frequency
of the mutation in Switzerland is explained by a founder effect of a relatively recent mutation event.
Received: 17 February 1997 / Accepted: 26 March 1977 相似文献
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Alessandra Gentilini Alessandra Caligiuri Chiara Raggi Krista Rombouts Massimo Pinzani Giulia Lori Margherita Correnti Pietro Invernizzi Elisabetta Rovida Nadia Navari Sabina Di Matteo Domenico Alvaro Jesus M. Banales Pedro Rodrigues Carlotta Raschioni Matteo Donadon Luca Di Tommaso Fabio Marra 《生物化学与生物物理学报:疾病的分子基础》2019,1865(9):2246-2256
Development of cholangiocarcinoma (CCA) is dependent on a cross-talk with stromal cells, which release different chemokines including CXCL12, that interacts with two different receptors, CXCR4 and CXCR7. The aim of the present study was to investigate the role of CXCR7 in CCA cells. CXCR7 is overexpressed by different CCA cell lines and in human CCA specimens. Knock-down of CXCR7 in HuCCT-1 cells reduced migration, invasion, and CXCL12-induced adhesion to collagen I. Survival of CCA was also reduced in CXCR7-silenced cells. The ability of CXCL12 to induce cell migration and survival was also blocked by CCX733, a CXCR7 antagonist. Similar effects of CXCR7 activation were observed in CCLP-1 cells and in primary iCCA cells. Enrichment of tumor stem-like cells by a 3D culture system resulted in increased CXCR7 expression compared to cells grown in monolayers, and genetic knockdown of CXCR7 robustly reduced sphere formation both in HuCCT-1 and in CCLP-1 cells. In HuCCT-1 cells CXCR7 was found to interact with β-arrestin 2, which was necessary to mediate CXCL12-induced migration, but not survival. In conclusion, CXCR7 is widely expressed in CCA, and contributes to the aggressive phenotype of CCA cells, inducing cell migration, invasion, adhesion, survival, growth and stem cell-like features. Cell migration induced by CXCR7 requires interaction with β-arrestin 2. 相似文献