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991.
992.
We have previously described a small molecule-directed protein dimerization strategy, using coumermycin to juxtapose Raf fusion proteins containing the coumermycin-binding domain GyrB. Oligomerization of cytoplasmically localized Raf-GyrB fusion proteins leads to an increase in the kinase activity of both Raf and its substrate Mek. Surprisingly, more distal targets, such as Erk1 and Erk2, are not activated using this approach. Here we report that coumermycin-induced oligomerization of a membrane-localized Raf-GyrB fusion protein potently activated Erk1 and Erk2, up-regulated Fos protein levels, and induced expression of many immediate-early response genes. Thus, both membrane localization and oligomerization of Raf-GyrB are required to target Raf signals to downstream effectors. The ability to activate the entire Raf signal transduction cascade conditionally, using coumermycin-induced oligomerization, should prove useful for dissecting Raf-mediated effects on gene expression and cellular differentiation. 相似文献
993.
994.
Tian L Nyman H Kilgannon P Yoshihara Y Mori K Andersson LC Kaukinen S Rauvala H Gallatin WM Gahmberg CG 《The Journal of cell biology》2000,150(1):243-252
Intercellular adhesion molecule-5 (ICAM-5) is a dendritically polarized membrane glycoprotein in telencephalic neurons, which shows heterophilic binding to leukocyte beta(2)-integrins. Here, we show that the human ICAM-5 protein interacts in a homophilic manner through the binding of the immunoglobulin domain 1 to domains 4-5. Surface coated ICAM-5-Fc promoted dendritic outgrowth and arborization of ICAM- 5-expressing hippocampal neurons. During dendritogenesis in developing rat brain, ICAM-5 was in monomer form, whereas in mature neurons it migrated as a high molecular weight complex. The findings indicate that its homophilic binding activity was regulated by nonmonomer/monomer transition. Thus, ICAM-5 displays two types of adhesion activity, homophilic binding between neurons and heterophilic binding between neurons and leukocytes. 相似文献
995.
次生栎林蒸腾强度与生态因子的关系 总被引:7,自引:0,他引:7
采用多元回归分析和灰色关联分析方法,探讨下蜀次生栎林蒸腾强度与生态因子的相关关系。研究认为用二次工咕次多项式回归方程和指数回归方程拟合更能反映各生态因子在整个生长季中与蒸腾强度关系的性质。影响蒸腾强度的主要生态因子是温度和净辐射;其次是空气相对湿度和土壤热流通量;风速和土壤含水率的影响很小。灰色关联分析与多元回归分析的结论一致。研究结果为进一步阐明次生栎林的结构和功能提供了理论基础。 相似文献
996.
997.
Mumm JS Schroeter EH Saxena MT Griesemer A Tian X Pan DJ Ray WJ Kopan R 《Molecular cell》2000,5(2):197-206
Gamma-secretase-like proteolysis at site 3 (S3), within the transmembrane domain, releases the Notch intracellular domain (NICD) and activates CSL-mediated Notch signaling. S3 processing occurs only in response to ligand binding; however, the molecular basis of this regulation is unknown. Here we demonstrate that ligand binding facilitates cleavage at a novel site (S2), within the extracellular juxtamembrane region, which serves to release ectodomain repression of NICD production. Cleavage at S2 generates a transient intermediate peptide termed NEXT (Notch extracellular truncation). NEXT accumulates when NICD production is blocked by point mutations or gamma-secretase inhibitors or by loss of presenilin 1, and inhibition of NEXT eliminates NICD production. Our data demonstrate that S2 cleavage is a ligand-regulated step in the proteolytic cascade leading to Notch activation. 相似文献
998.
Quaroni A Tian JQ Seth P Ap Rhys C 《American journal of physiology. Cell physiology》2000,279(4):C1045-C1057
Constant renewal of the intestinal epitheliumis a highly coordinated process that has been subject to intenseinvestigation, but its regulatory mechanisms are still essentiallyunknown. In this study, we have demonstrated that forced expression ofthe cyclin-dependent kinase inhibitors (CKIs) p27Kip1 andp21Cip1/WAF1 in human intestinal epithelial cells led toexpression of differentiation markers at both the mRNA and proteinlevels. Cell differentiation was temporally dissociated from inhibitionof retinoblastoma protein phosphorylation and growth arrest, alreadyestablished 1 day after infection with recombinant adenoviruses.p27Kip1 proved significantly more efficient thanp21Cip1/WAF1 in induction of cell differentiation. Incontrast, forced expression of p16INK4a resulted in growtharrest without induction of differentiation markers. These resultsimplicate both p27Kip1 and p21Cip1/WAF1 in thedifferentiation-timing process, but p21Cip1/WAF1 may actindirectly by increasing p27Kip1 levels. These results alsosuggest that induction of intestinal epithelial cell differentiation byCKIs is not related to their effects on the cell cycle and may involveinteractions with cellular components other than cyclins andcyclin-dependent kinases. 相似文献
999.
Ligation of cell surface matrix adhesion receptors such as integrins can increase expression of specific cell cycle regulatory proteins such as cyclin A, thereby regulating cell cycle progression. Disruption of cell surface matrix receptor interaction with the extracellular matrix can trigger apoptosis. Induction of apoptosis has been linked to unscheduled up-regulation of cyclin A and activation of cyclin-A-associated dependent kinase 2 activity due to cleavage of cyclin-dependent kinase inhibitors by caspases. We have found that ligation of the cell surface matrix adhesion receptor CD44 by anti-CD44 antibody induces cell detachment and triggers apoptosis. In this report we show that ligation of CD44 by anti-CD44 antibody increases the expression of cyclin A protein prior to activation of caspase-3-like activity and morphological changes of apoptosis. Down-regulation of cyclin A protein levels by cyclin A antisense oligonucleotides dramatically decreased fibroblast apoptosis in response to anti-CD44 antibody. These data identify an important functional role of cyclin A in the induction of fibroblast apoptosis due to the ligation of the cell surface adhesion receptor CD44 by anti-CD44 antibody. 相似文献
1000.
The N-terminal fragment of adenosine diphosphate (ADP) ribosylation factor 1 (ARF1) is proposed to be involved in the guanosine triphosphate- (GTP-) dependent, reversible association of the protein with membranes through the interaction of not only the N-linked myristoyl chain but also its highly conserved N-terminal hydrophobic residues. Based on the N-terminal sequence of this protein, specifically (13)C- and (15)N-labeled peptides were synthesized with and without an N-myristoyl anchor. The behavior, including structure, dynamics, and orientation, of these peptides in a lipid environment was then studied through a combination of solution (1)H nuclear magnetic resonance (NMR) techniques in micelles and heteronuclear solid-state NMR experiments in magnetically aligned bicelles. The work presented is an extension of the previously reported characterization of the myristoylated N-terminal fragment of ARF1 [Losonczi and Prestegard (1998) Biochemistry 37, 706-716] to include a comparison to a nonmyristoylated analogue. Results indicate that both myristoylated and nonmyristoylated peptides are alpha-helical in a lipid environment and that N-myristoylation does not greatly influence the structure of the peptides. Evidence is presented suggesting association of the peptides with bilayer disks through a combination of edge and surface interactions. 相似文献