全文获取类型
收费全文 | 3505篇 |
免费 | 462篇 |
国内免费 | 2篇 |
专业分类
3969篇 |
出版年
2021年 | 46篇 |
2020年 | 29篇 |
2019年 | 34篇 |
2018年 | 44篇 |
2017年 | 39篇 |
2016年 | 76篇 |
2015年 | 119篇 |
2014年 | 109篇 |
2013年 | 139篇 |
2012年 | 159篇 |
2011年 | 191篇 |
2010年 | 112篇 |
2009年 | 88篇 |
2008年 | 137篇 |
2007年 | 158篇 |
2006年 | 126篇 |
2005年 | 123篇 |
2004年 | 122篇 |
2003年 | 122篇 |
2002年 | 153篇 |
2001年 | 129篇 |
2000年 | 119篇 |
1999年 | 98篇 |
1998年 | 65篇 |
1997年 | 57篇 |
1996年 | 49篇 |
1995年 | 41篇 |
1994年 | 34篇 |
1993年 | 34篇 |
1992年 | 76篇 |
1991年 | 77篇 |
1990年 | 50篇 |
1989年 | 56篇 |
1988年 | 46篇 |
1987年 | 55篇 |
1986年 | 34篇 |
1985年 | 47篇 |
1984年 | 37篇 |
1983年 | 30篇 |
1982年 | 29篇 |
1981年 | 36篇 |
1980年 | 41篇 |
1979年 | 35篇 |
1978年 | 39篇 |
1977年 | 33篇 |
1976年 | 26篇 |
1975年 | 40篇 |
1974年 | 39篇 |
1973年 | 30篇 |
1972年 | 27篇 |
排序方式: 共有3969条查询结果,搜索用时 15 毫秒
61.
The septins constitute a family of filament-forming proteins ubiquitous in eukaryotic species. We demonstrate here that the Saccharomyces cerevisiae septin, Cdc3, is a substrate of the cell cycle regulatory cyclin-dependent kinase (Cdk), Cdc28. Two serines near the C-terminus of Cdc3 are phosphorylated in a Cdc28-dependent manner. Analysis of a mutant allele that cannot be phosphorylated at these sites revealed an effect of Cdc28 phosphorylation of Cdc3 at the time of budding. Immunofluorescence analysis of wild-type and mutant Cdc3 indicated that prevention of phosphorylation at Cdc28-dependent sites impairs the disassembly of the old septin ring, which is inherited at mitosis but which usually disappears immediately prior to assembly of a new ring. Furthermore, immuno-fluorescence analysis of septin ring dynamics in a G1 cyclin (Cln) mutant suggests that G1 cyclin function is required for efficient ring disassembly. Thus, phosphorylation of Cdc3 by the Cdc28 kinase at the end of G1 may facilitate initiation of a new cell cycle by promoting disassembly of the obsolete septin ring from the previous cell cycle. 相似文献
62.
Billam P Bonaparte KL Liu J Ruckwardt TJ Chen M Ryder AB Wang R Dash P Thomas PG Graham BS 《The Journal of biological chemistry》2011,286(6):4829-4841
CD8+ T cell responses are important for recognizing and resolving viral infections. To better understand the selection and hierarchy of virus-specific T cell responses, we compared the T cell receptor (TCR) clonotype in parent and hybrid strains of respiratory syncytial virus-infected mice. K(d)M2(82-90) (SYIGSINNI) in BALB/c and D(b)M(187-195) (NAITNAKII) in C57Bl/6 are both dominant epitopes in parent strains but assume a distinct hierarchy, with K(d)M2(82-90) dominant to D(b)M(187-195) in hybrid CB6F1/J mice. The dominant K(d)M2(82-90) response is relatively public and is restricted primarily to the highly prevalent Vβ13.2 in BALB/c and hybrid mice, whereas D(b)M(187-195) responses in C57BL/6 mice are relatively private and involve multiple Vβ subtypes, some of which are lost in hybrids. A significant frequency of TCR CDR3 sequences in the D(b)M(187-195) response have a distinct "(D/E)WG" motif formed by a limited number of recombination strategies. Modeling of the dominant epitope suggested a flat, featureless structure, but D(b)M(187-195) showed a distinctive structure formed by Lys(7). The data suggest that common recombination events in prevalent Vβ genes may provide a numerical advantage in the T cell response and that distinct epitope structures may impose more limited options for successful TCR selection. Defining how epitope structure is interpreted to inform T cell function will improve the design of future gene-based vaccines. 相似文献
63.
The Cks/Suc1 proteins associate with CDK/cyclin complexes, but their precise function(s) is not well defined. Here we demonstrate that Cks1 directs the ubiquitin-mediated proteolysis of the CDK-bound substrate p27Kip1 by the protein ubiquitin ligase (E3) SCF(Skp2). Cks1 associates with the F box protein Skp2 and is essential for recognition of the p27Kip1 substrate for ubiquitination in vivo and in vitro. Using purified recombinant proteins, we reconstituted p27Kip1 ubiquitination activity and show that it is dependent on Cks1. CKS1-/- mice are abnormally small, and cells derived from them proliferate poorly, particularly under limiting mitogen conditions, possibly due to elevated levels of p27Kip1. 相似文献
64.
65.
Five chemotherapeutic agents which inhibit mitosis caused an effect on the colchicine bound to the isolated tubulin from mouse lymphoma L5178Y cells. These effects were examined over a time course of 4, 12, 24, 48, and 72 hours after a single administration of each drug. Vinblastine, oncodazole, and bleomycin decreased the amount of colchicine bound per mg protein; procarbazine and chloroambucil increased the amount bound. All of the drugs except procarbazine required more than 4 hours to cause an effect on colchicine binding and in the case of bleomycin and oncodazole some recovery occurred after 48 hours. The mitotic index was affected by 4 hours by all drugs: procarbazine, chlorambucil and bleomycin caused a decrease; vinblastine and oncodazole, an increase. 相似文献
66.
Evidence is presented to show that “Caucasian” genes (B, K, Lua, r, AK2, Pc, and Gm3,5,11) in hybrid North American Indian populations follow a Poisson distribution. A method of determining the maximum amount of admixture, given an observed count of Caucasian genes, is developed. Establishment of the upper limit of admixture is suggested as the preferred estimate of gene flow in situations where absence of specific genes at particular loci precludes the calculation of a mean admixture estimate. 相似文献
67.
G Kim Prisk Harold J B Guy John B West James W Reed 《Journal of applied physiology》2003,94(3):1186-1192
The analysis of the gas in a single expirate has long been used to estimate the degree of ventilation-perfusion (Va/Q) inequality in the lung. To further validate this estimate, we examined three measures of Va/Q inhomogeneity calculated from a single full exhalation in nine anesthetized mongrel dogs under control conditions and after exposure to aerosolized methacholine. These measurements were then compared with arterial blood gases and with measurements of Va/Q inhomogeneity obtained using the multiple inert gas elimination technique. The slope of the instantaneous respiratory exchange ratio (R slope) vs. expired volume was poorly correlated with independent measures, probably because of the curvilinear nature of the relationship due to continuing gas exchange. When R was converted to the intrabreath Va/Q (iV/Q), the best index was the slope of iV/Q vs. volume over phase III (iV/Q slope). This was strongly correlated with independent measures, especially those relating to inhomogeneity of perfusion. The correlations for iV/Q slope and R slope considerably improved when only the first half of phase III was considered. We conclude that a useful noninvasive measurement of Va/Q inhomogeneity can be derived from the intrabreath respiratory exchange ratio. 相似文献
68.
69.
Monoclonal antibody OKT11A inhibits and recombinant interleukin 2 (IL 2) augments expression of IL 2 receptors at a pretranslational level 总被引:3,自引:0,他引:3
J C Reed W C Greene R G Hoover P C Nowell 《Journal of immunology (Baltimore, Md. : 1950)》1985,135(4):2478-2482
The expression of receptors for interleukin 2 (IL 2) represents a critical event regulating the growth of normal T lymphocytes. We investigated the effects of the inhibitory monoclonal antibody OKT11A (anti-sheep erythrocyte receptor) and of purified recombinant IL 2 (rIL 2) on the expression of IL 2 receptors by activated T cells at both the protein and the mRNA levels. Adding OKT11A antibody (0.5 microgram/ml) to phytohemagglutinin (PHA)-stimulated cultures of human peripheral blood mononuclear cells (PBMC) markedly suppressed cellular proliferation (assessed by [3H]thymidine incorporation) and IL 2 receptor expression (determined by immunofluorescence assay by using the anti-IL 2-receptor antibody, anti-Tac). Northern blot analysis performed with the use of a cDNA probe specific for the human IL 2 receptor gene demonstrated that OKT11A antibody also decreased the accumulation of IL 2 receptor mRNA induced by PHA in PBMC. Purified rIL 2 (10 U/ml) alone had little effect on the expression of IL 2 receptors in unstimulated PBMC cultures. In combination with PHA or with PHA plus OKT11A, however, rIL 2 augmented both the expression of IL 2 receptor protein on PBMC and the accumulation of IL 2 receptor mRNA in PBMC. Adding anti-Tac antibody to PBMC cultures to block the interaction of IL 2 with its receptor diminished the accumulation of IL 2 receptor mRNA induced by PHA. Taken together, these data demonstrate that OKT11A antibody inhibits and IL 2 augments expression of IL 2 receptors on PHA-stimulated T cells, at least in part, at a pretranslational level. 相似文献
70.