全文获取类型
收费全文 | 932篇 |
免费 | 113篇 |
出版年
2021年 | 23篇 |
2020年 | 10篇 |
2019年 | 7篇 |
2018年 | 11篇 |
2016年 | 6篇 |
2015年 | 33篇 |
2014年 | 17篇 |
2013年 | 26篇 |
2012年 | 33篇 |
2011年 | 38篇 |
2010年 | 28篇 |
2009年 | 30篇 |
2008年 | 31篇 |
2007年 | 47篇 |
2006年 | 43篇 |
2005年 | 29篇 |
2004年 | 27篇 |
2003年 | 39篇 |
2002年 | 31篇 |
2001年 | 29篇 |
2000年 | 35篇 |
1999年 | 27篇 |
1998年 | 23篇 |
1997年 | 17篇 |
1996年 | 14篇 |
1995年 | 9篇 |
1994年 | 10篇 |
1993年 | 11篇 |
1992年 | 41篇 |
1991年 | 24篇 |
1990年 | 32篇 |
1989年 | 22篇 |
1988年 | 19篇 |
1987年 | 19篇 |
1986年 | 20篇 |
1985年 | 14篇 |
1984年 | 15篇 |
1983年 | 18篇 |
1982年 | 11篇 |
1981年 | 11篇 |
1980年 | 10篇 |
1979年 | 7篇 |
1978年 | 13篇 |
1975年 | 5篇 |
1974年 | 13篇 |
1973年 | 10篇 |
1972年 | 10篇 |
1971年 | 5篇 |
1970年 | 8篇 |
1968年 | 5篇 |
排序方式: 共有1045条查询结果,搜索用时 15 毫秒
81.
82.
83.
84.
Regulation of vasodilator-stimulated phosphoprotein phosphorylation and interaction with Abl by protein kinase A and cell adhesion 总被引:10,自引:0,他引:10
Members of the vasodilator-stimulated phosphoprotein (VASP) family are important regulators of actin cytoskeletal dynamics whose functions and protein-protein interactions are regulated by phosphorylation by the cAMP-dependent protein kinase (PKA). Herein, we show that phosphorylation of VASP is dynamically regulated by cellular adhesion to extracellular matrix. Detachment of cells stimulated PKA activity and induced PKA-dependent phosphorylation of VASP and the related murine-Enabled (Mena) protein. VASP and Mena were rapidly dephosphorylated immediately following reattachment but showed an intermediate level of phosphorylation during active cell spreading. This pattern correlated closely with adhesion-dependent changes in PKA activity. The in vivo interaction of VASP with the Abl tyrosine kinase, shown here for the first time, was readily apparent in adherent cells, lost following cellular detachment, and induced upon reattachment to matrix. Importantly, inhibition of PKA activity prevented phosphorylation of VASP and dissociation of VASP-Abl complexes after cellular detachment, whereas activation of PKA completely eliminated the co-immunoprecipitation of Abl activity with VASP. These data establish a new biochemical link between cell adhesion and regulation of VASP proteins and provide the first demonstration of a regulated interaction between VASP and Abl in mammalian cells. 相似文献
85.
Lymphotoxin-alpha-deficient mice make delayed,but effective,T and B cell responses to influenza 总被引:6,自引:0,他引:6
Lund FE Partida-Sánchez S Lee BO Kusser KL Hartson L Hogan RJ Woodland DL Randall TD 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(9):5236-5243
Lymphotoxin-alpha(-/-) (LTalpha(-/-)) mice are thought to be unable to generate effective T and B cell responses. This is attributed to the lack of lymph nodes and the disrupted splenic architecture of these mice. However, despite these defects we found that LTalpha(-/-) mice could survive infection with a virulent influenza A virus. LTalpha(-/-) mice and normal wild-type mice infected with influenza A generated similar numbers of influenza-specific CD8 T cells that were able to produce IFN-gamma and kill target cells presenting influenza peptides. Furthermore influenza-infected LTalpha(-/-) mice produced high titers of influenza-specific IgM, IgG, and IgA. However, both CD8 and B cell immune responses were delayed in LTalpha(-/-) mice by 2-3 days. The delayed cellular and humoral immune response was sufficient to mediate viral clearance in LTalpha(-/-) mice that were infected with relatively low doses of influenza virus. However, when LTalpha(-/-) mice were infected with larger doses of influenza, they succumbed to infection before the immune response was initiated. These results demonstrate that neither LTalpha nor constitutively organized lymphoid tissues, such as lymph nodes and spleen, are absolutely required for the generation of effective immunity against the respiratory virus influenza A. However, the presence of LTalpha and/or lymph nodes does accelerate the initiation of immune responses, which leads to protection from larger doses of virus. 相似文献
86.
87.
88.
In vivo dissection of the chromosome condensation machinery: reversibility of condensation distinguishes contributions of condensin and cohesin 下载免费PDF全文
The machinery mediating chromosome condensation is poorly understood. To begin to dissect the in vivo function(s) of individual components, we monitored mitotic chromosome structure in mutants of condensin, cohesin, histone H3, and topoisomerase II (topo II). In budding yeast, both condensation establishment and maintenance require all of the condensin subunits, but not topo II activity or phospho-histone H3. Structural maintenance of chromosome (SMC) protein 2, as well as each of the three non-SMC proteins (Ycg1p, Ycs4p, and Brn1p), was required for chromatin binding of the condensin complex in vivo. Using reversible condensin alleles, we show that chromosome condensation does not involve an irreversible modification of condensin or chromosomes. Finally, we provide the first evidence of a mechanistic link between condensin and cohesin function. A model discussing the functional interplay between cohesin and condensin is presented. 相似文献
89.
Hong YS Hogan JR Wang X Sarkar A Sim C Loftus BJ Ren C Huff ER Carlile JL Black K Zhang HB Gardner MJ Collins FH 《Molecular genetics and genomics : MGG》2003,268(6):720-728
A Bacterial Artificial Chromosome (BAC) genomic DNA library of Anopheles gambiae, the major human malaria vector in sub-Saharan Africa, was constructed and characterized. This library (ND-TAM) is composed of 30,720 BAC clones in eighty 384-well plates. The estimated average insert size of the library is 133 kb, with an overall genome coverage of approximately 14-fold. The ends of approximately two-thirds of the clones in the library were sequenced, yielding 32,340 pair-mate ends. A statistical analysis (G-test) of the results of PCR screening of the library indicated a random distribution of BACs in the genome, although one gap encompassing the white locus on the X-chromosome was identified. Furthermore, combined with another previously constructed BAC library (ND-1), ~2,000 BACs have been physically mapped by polytene chromosomal in situ hybridization. These BAC end pair mates and physically mapped BACs have been useful for both the assembly of a fully sequenced A. gambiae genome and for linking the assembled sequence to the three polytene chromosomes. This ND-TAM library is now publicly available at both http://www.malaria.mr4.org/mr4pages/index.html/ and http://hbz.tamu.edu/, providing a valuable resource to the mosquito research community. 相似文献
90.
Jin L Sliz P Chen L Macián F Rao A Hogan PG Harrison SC 《Nature structural biology》2003,10(10):807-811
The crystal structure of the NFAT1 Rel homology region (RHR) bound to a pseudo-palindromic DNA site reveals an asymmetric dimer interaction between the RHR-C domains, unrelated to the contact seen in Rel dimers such as NF kappa B. Binding studies with a form of the NFAT1 RHR defective in the dimer contact show loss of cooperativity and demonstrate that the same interaction is present in solution. The structure we have determined may correspond to a functional NFAT binding mode at palindromic sites of genes induced during the anergic response to weak TCR signaling. 相似文献