全文获取类型
收费全文 | 2693篇 |
免费 | 254篇 |
出版年
2023年 | 6篇 |
2022年 | 16篇 |
2021年 | 36篇 |
2020年 | 23篇 |
2019年 | 36篇 |
2018年 | 59篇 |
2017年 | 44篇 |
2016年 | 86篇 |
2015年 | 115篇 |
2014年 | 135篇 |
2013年 | 148篇 |
2012年 | 198篇 |
2011年 | 198篇 |
2010年 | 150篇 |
2009年 | 138篇 |
2008年 | 176篇 |
2007年 | 166篇 |
2006年 | 133篇 |
2005年 | 130篇 |
2004年 | 135篇 |
2003年 | 140篇 |
2002年 | 129篇 |
2001年 | 24篇 |
2000年 | 18篇 |
1999年 | 27篇 |
1998年 | 36篇 |
1997年 | 33篇 |
1996年 | 30篇 |
1995年 | 40篇 |
1994年 | 26篇 |
1993年 | 36篇 |
1992年 | 34篇 |
1991年 | 22篇 |
1990年 | 21篇 |
1989年 | 24篇 |
1988年 | 20篇 |
1987年 | 9篇 |
1986年 | 11篇 |
1985年 | 14篇 |
1984年 | 10篇 |
1983年 | 9篇 |
1982年 | 10篇 |
1981年 | 13篇 |
1980年 | 11篇 |
1979年 | 6篇 |
1978年 | 10篇 |
1977年 | 11篇 |
1975年 | 6篇 |
1972年 | 6篇 |
1970年 | 7篇 |
排序方式: 共有2947条查询结果,搜索用时 531 毫秒
161.
Fournier HN Dupé-Manet S Bouvard D Lacombe ML Marie C Block MR Albiges-Rizo C 《The Journal of biological chemistry》2002,277(23):20895-20902
Cell adhesion-dependent signaling implicates cytoplasmic proteins interacting with the intracellular tails of integrins. Among those, the integrin cytoplasmic domain-associated protein 1alpha (ICAP-1alpha) has been shown to interact specifically with the beta(1) integrin cytoplasmic domain. Although it is likely that this protein plays an important role in controlling cell adhesion and migration, little is known about its actual function. To search for potential ICAP-1alpha-binding proteins, we used a yeast two-hybrid screen and identified the human metastatic suppressor protein nm23-H2 as a new partner of ICAP-1alpha. This direct interaction was confirmed in vitro, using purified recombinant ICAP-1alpha and nm23-H2, and by co-immunoprecipitation from CHO cell lysates over-expressing ICAP-1alpha. The physiological relevance of this interaction is provided by confocal fluorescence microscopy, which shows that ICAP-1alpha and nm23-H2 are co-localized in lamellipodia during the early stages of cell spreading. These adhesion sites are enriched in occupied beta(1) integrins and precede the formation of focal adhesions devoid of ICAP-1alpha and nm23-H2, indicating the dynamic segregation of components of matrix adhesions. This peripheral staining of ICAP-1alpha and nm23-H2 is only observed in cells spreading on fibronectin and collagen and is absent in cells spreading on poly-l-lysine, vitronectin, or laminin. This is consistent with the fact that targeting of both ICAP-1alpha and nm23-H2 to the cell periphery is dependent on beta(1) integrin engagement rather than being a consequence of cell adhesion. This finding represents the first evidence that the tumor suppressor nm23-H2 could act on beta(1) integrin-mediated cell adhesion by interacting with one of the integrin partners, ICAP-1alpha. 相似文献
162.
163.
Duchene J Schanstra JP Pecher C Pizard A Susini C Esteve JP Bascands JL Girolami JP 《The Journal of biological chemistry》2002,277(43):40375-40383
Mitogenic G protein-coupled receptor (GPCR) signaling has been extensively studied. In contrast, little is known about anti-mitogenic GPCR signaling. We show here that anti-mitogenic signaling of a GPCR, the bradykinin B2 receptor, involves a novel direct protein-protein interaction. The antiproliferative effect of bradykinin was accompanied by a transient increase in protein-tyrosine phosphatase activity. Using surface plasmon resonance analysis, we observed that an immunoreceptor tyrosine-based inhibitory motif (ITIM) located in the C-terminal part of the B2 receptor interacted specifically with the protein-tyrosine phosphatase SHP-2. The interaction was confirmed in primary culture renal mesangial cells by co-immunoprecipitation of a B2 receptor.SHP-2 complex. The extent of the interaction was transiently increased by stimulation with bradykinin, which was accompanied by an increase in specific SHP-2 phosphatase activity. Mutational analysis of the key ITIM residue confirmed that the B2 receptor ITIM sequence is required for interaction with SHP-2, SHP-2 activation, and the anti-mitogenic effect of bradykinin. Finally, in mesangial cells transfected with a dominant-negative form of SHP-2, bradykinin lost the ability to inhibit cell proliferation. These observations demonstrate that bradykinin inhibits cell proliferation by a novel mechanism involving a direct protein-protein interaction between a GPCR (the B2 receptor) and SHP-2. 相似文献
164.
165.
166.
Five Ca(2+)-independent protein kinases were rapidly activated by hypoosmotic stress, moderate or high hyperosmolarity induced by several osmolytes, sucrose, mannitol or NaCl. Three of these kinases, transiently activated by hypoosmolarity, recognised by anti-phosphorylated mitogen-activated protein (MAP) kinase antibodies, sensitive to a MAP kinase inhibitor and inactivated by the action of a tyrosine phosphatase, corresponded to MAP kinases. Using specific antibodies, two of the MAP kinases were identified as AtMPK6 and AtMPK3. The two other protein kinases, durably activated by high hyperosmolarity, did not belong to the MAP kinase family. Activation of AtMPK6 and AtMPK3 by hypoosmolarity depended on upstream protein kinases sensitive to staurosporine and on calcium influx. In contrast, these two transduction steps were not involved in the activation of the two protein kinases activated by high hyperosmolarity. 相似文献
167.
Cold sweetening in diploid potato: mapping quantitative trait loci and candidate genes 总被引:16,自引:0,他引:16
Menéndez CM Ritter E Schäfer-Pregl R Walkemeier B Kalde A Salamini F Gebhardt C 《Genetics》2002,162(3):1423-1434
A candidate gene approach has been used as a first step to identify the molecular basis of quantitative trait variation in potato. Sugar content of tubers upon cold storage was the model trait chosen because the metabolic pathways involved in starch and sugar metabolism are well known and many of the genes have been cloned. Tubers of two F(1) populations of diploid potato grown in six environments were evaluated for sugar content after cold storage. The populations were genotyped with RFLP, AFLP, and candidate gene markers. QTL analysis revealed that QTL for glucose, fructose, and sucrose content were located on all potato chromosomes. Most QTL for glucose content mapped to the same positions as QTL for fructose content. QTL explaining >10% of the variability for reducing sugars were located on linkage groups I, III, VII, VIII, IX, and XI. QTL consistent across populations and/or environments were identified. QTL were linked to genes encoding invertase, sucrose synthase 3, sucrose phosphate synthase, ADP-glucose pyrophosphorylase, sucrose transporter 1, and a putative sucrose sensor. The results suggest that allelic variants of enzymes operating in carbohydrate metabolic pathways contribute to the genetic variation in cold sweetening. 相似文献
168.
We have previously shown that regulatory CD25(+)CD4(+) T cells are resistant to clonal deletion induced by viral superantigen in vivo. In this work we report that isolated CD25(+)CD4(+) T cells activated in vitro by anti-CD3 Ab are resistant to Fas-induced apoptosis, in contrast to their CD25(-)CD4(+) counterparts. Resistance of CD25(+)CD4(+) T cells to Fas-dependent activation-induced cell death is not linked to their inability to produce IL-2 or to their ability to produce IL-10. The sensitivity of both populations to Fas-induced apoptosis can be modulated in vitro by changing the CD25(+)CD4(+):CD25(-)CD4(+) T cell ratio. The sensitivity of CD25(-)CD4(+) T cells to apoptosis can be reduced, while the sensitivity of CD25(+)CD4(+) T cells can be enhanced. Modulation of Fas-dependent apoptosis is associated with changes in cytokine production. However, while CD25(-)CD4(+) T cell apoptosis is highly dependent on IL-2 (production of which is inhibited by CD25(+)CD4(+) T cells in coculture), modulation of CD25(+)CD4(+) T cell apoptosis is IL-2 independent. Taken together, these results suggest that CD25(+)CD4(+) and CD25(-)CD4(+) T cell sensitivity to Fas-dependent apoptosis is dynamically modulated during immune responses; this modulation appears to help maintain a permanent population of regulatory T cells required to control effector T cells. 相似文献
169.
170.