全文获取类型
收费全文 | 67242篇 |
免费 | 5687篇 |
国内免费 | 16篇 |
出版年
2023年 | 344篇 |
2022年 | 417篇 |
2021年 | 880篇 |
2020年 | 561篇 |
2019年 | 659篇 |
2018年 | 1337篇 |
2017年 | 1272篇 |
2016年 | 1586篇 |
2015年 | 1897篇 |
2014年 | 2122篇 |
2013年 | 3285篇 |
2012年 | 4705篇 |
2011年 | 5039篇 |
2010年 | 2772篇 |
2009年 | 1998篇 |
2008年 | 4074篇 |
2007年 | 4131篇 |
2006年 | 3799篇 |
2005年 | 3463篇 |
2004年 | 3281篇 |
2003年 | 3062篇 |
2002年 | 3019篇 |
2001年 | 1806篇 |
2000年 | 2043篇 |
1999年 | 1191篇 |
1998年 | 625篇 |
1997年 | 494篇 |
1996年 | 548篇 |
1995年 | 479篇 |
1994年 | 519篇 |
1993年 | 469篇 |
1992年 | 562篇 |
1991年 | 504篇 |
1990年 | 458篇 |
1989年 | 389篇 |
1988年 | 413篇 |
1987年 | 375篇 |
1986年 | 333篇 |
1985年 | 455篇 |
1984年 | 517篇 |
1983年 | 431篇 |
1982年 | 424篇 |
1981年 | 398篇 |
1980年 | 345篇 |
1979年 | 381篇 |
1978年 | 339篇 |
1977年 | 342篇 |
1976年 | 326篇 |
1975年 | 386篇 |
1973年 | 290篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
91.
92.
Neural crest cell differentiation is responsive to a variety of extrinsic signals that include extracellular matrix (ECM) molecules and growth factors. Transforming growth factor-beta (TGF-beta) has diverse, cell type-specific effects, many of which involve regulation of synthesis of ECM molecules and their cell surface receptors. We are studying both separate and potentially interrelated influences of ECM and growth factors on crest differentiation and report here that TGF-beta alters several aspects of crest cell behavior in vitro. Clusters of quail neural crest cells were cultured in the presence and absence of 400 pM TGF-beta 1 and examined at 1, 3, and 5 days. When examined at 5 days, there was a dramatic decrease in the number of melanocytes in treated cultures, regardless of the onset or duration of TGF-beta treatment. With continuous TGF-beta treatment, or with treatment only during crest cluster formation on explanted neural tubes, many cells increased in area, becoming extremely flat. These changes were evident beginning on Day 3. While quantitative analyses of video images documented the size increase, several aspects of motility were relatively unchanged. Synthesis of fibronectin (FN) by approximately 11% of cells on Day 3 and 31% of cells on Day 5 was demonstrated by immunocytochemistry and was associated with a sixfold increase in FN mRNA by Day 5. Experiments which correlated FN immunoreactivity with incorporation of bromodeoxyuridine suggested that the population of large, flat, FN-positive cells did not proliferate selectively and that there was a slower rate of proliferation in TGF-beta-treated cultures than in untreated cultures. The large FN-immunoreactive cells resemble cells derived from cephalic neural crest and raise interesting questions concerning potential roles for TGF-beta in regulating crest differentiation in vivo. 相似文献
93.
94.
95.
96.
Michaela Ludolphs Daniela Schneeberger Tolga Soykan Jonas Sch?fer Theofilos Papadopoulos Nils Brose Hermann Schindelin Claudia Steinem 《The Journal of biological chemistry》2016,291(1):244-254
The regulatory protein collybistin (CB) recruits the receptor-scaffolding protein gephyrin to mammalian inhibitory glycinergic and GABAergic postsynaptic membranes in nerve cells. CB is tethered to the membrane via phosphoinositides. We developed an in vitro assay based on solid-supported 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine membranes doped with different phosphoinositides on silicon/silicon dioxide substrates to quantify the binding of various CB2 constructs using reflectometric interference spectroscopy. Based on adsorption isotherms, we obtained dissociation constants and binding capacities of the membranes. Our results show that full-length CB2 harboring the N-terminal Src homology 3 (SH3) domain (CB2SH3+) adopts a closed and autoinhibited conformation that largely prevents membrane binding. This autoinhibition is relieved upon introduction of the W24A/E262A mutation, which conformationally “opens” CB2SH3+ and allows the pleckstrin homology domain to properly bind lipids depending on the phosphoinositide species with a preference for phosphatidylinositol 3-monophosphate and phosphatidylinositol 4-monophosphate. This type of membrane tethering under the control of the release of the SH3 domain of CB is essential for regulating gephyrin clustering. 相似文献
97.
98.
Alexander F. Christensen 《Global Ecology and Biogeography》2000,9(5):415-420
Historical evidence indicates that Great‐tailed Grackles colonized the Basin of Mexico from the Gulf Coast lowlands in the fifteenth century. They were probably assisted by an intentional introduction, but colonization succeeded because of anthropogenic habitat alterations over the previous two centuries. During the Colonial period, grackles withdrew from the Basin, only to recolonize it in recent decades. This withdrawal was also due probably to changes in land use, including drainage of much of the water from the Basin's lakes. 相似文献
99.
Continuous coenzyme dependent stereoselective synthesis of sulcatol by alcohol dehydrogenase 总被引:2,自引:0,他引:2
Summary 6-methyl-5-hepten-2-one was reduced to sulcatol ((+)-6-methyl-5-hepten-2-ol) by using alcohol dehydrogenase fromThermoanaerobium brockii in a continuous process. The cofactor NADP(H) was retained by a charged UF-membrane and regenerated by oxidation of isopropanol to acetone. Use of native NADP in a charged UF-membrane reactor proved to be superior to use of PEG coupled NADP in a uncharged UF-membrane reactor. 相似文献
100.
George V. Sharonov Eduard V. Bocharov Peter M. Kolosov Maria V. Astapova Alexander S. Arseniev Alexey V. Feofanov 《The Journal of biological chemistry》2014,289(21):14955-14964
The EphA2 receptor tyrosine kinase plays a central role in the regulation of cell adhesion and guidance in many human tissues. The activation of EphA2 occurs after proper dimerization/oligomerization in the plasma membrane, which occurs with the participation of extracellular and cytoplasmic domains. Our study revealed that the isolated transmembrane domain (TMD) of EphA2 embedded into the lipid bicelle dimerized via the heptad repeat motif L535X3G539X2A542X3V546X2L549 rather than through the alternative glycine zipper motif A536X3G540X3G544 (typical for TMD dimerization in many proteins). To evaluate the significance of TMD interactions for full-length EphA2, we substituted key residues in the heptad repeat motif (HR variant: G539I, A542I, G553I) or in the glycine zipper motif (GZ variant: G540I, G544I) and expressed YFP-tagged EphA2 (WT, HR, and GZ variants) in HEK293T cells. Confocal microscopy revealed a similar distribution of all EphA2-YFP variants in cells. The expression of EphA2-YFP variants and their kinase activity (phosphorylation of Tyr588 and/or Tyr594) and ephrin-A3 binding were analyzed with flow cytometry on a single cell basis. Activation of any EphA2 variant is found to occur even without ephrin stimulation when the EphA2 content in cells is sufficiently high. Ephrin-A3 binding is not affected in mutant variants. Mutations in the TMD have a significant effect on EphA2 activity. Both ligand-dependent and ligand-independent activities are enhanced for the HR variant and reduced for the GZ variant compared with the WT. These findings allow us to suggest TMD dimerization switching between the heptad repeat and glycine zipper motifs, corresponding to inactive and active receptor states, respectively, as a mechanism underlying EphA2 signal transduction. 相似文献