全文获取类型
收费全文 | 1816篇 |
免费 | 203篇 |
出版年
2022年 | 7篇 |
2021年 | 30篇 |
2020年 | 16篇 |
2019年 | 18篇 |
2018年 | 35篇 |
2017年 | 19篇 |
2016年 | 40篇 |
2015年 | 58篇 |
2014年 | 87篇 |
2013年 | 96篇 |
2012年 | 153篇 |
2011年 | 111篇 |
2010年 | 81篇 |
2009年 | 78篇 |
2008年 | 113篇 |
2007年 | 93篇 |
2006年 | 76篇 |
2005年 | 91篇 |
2004年 | 87篇 |
2003年 | 98篇 |
2002年 | 96篇 |
2001年 | 39篇 |
2000年 | 39篇 |
1999年 | 41篇 |
1998年 | 27篇 |
1997年 | 23篇 |
1996年 | 16篇 |
1995年 | 11篇 |
1994年 | 10篇 |
1993年 | 15篇 |
1992年 | 29篇 |
1991年 | 22篇 |
1990年 | 34篇 |
1989年 | 30篇 |
1988年 | 20篇 |
1987年 | 12篇 |
1986年 | 21篇 |
1985年 | 17篇 |
1984年 | 18篇 |
1983年 | 13篇 |
1982年 | 9篇 |
1981年 | 7篇 |
1980年 | 8篇 |
1979年 | 12篇 |
1978年 | 10篇 |
1977年 | 6篇 |
1976年 | 9篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1973年 | 6篇 |
排序方式: 共有2019条查询结果,搜索用时 15 毫秒
81.
82.
83.
The family of mammalian Sirtuin proteins comprises seven members homologous to yeast Sir2. Here we show that SIRT2, a cytoplasmic sirtuin, is the most abundant sirtuin in adipocytes. Sirt2 expression is downregulated during preadipocyte differentiation in 3T3-L1 cells. Overexpression of SIRT2 inhibits differentiation, whereas reducing SIRT2 expression promotes adipogenesis. Both effects are accompanied by corresponding changes in the expression of PPARgamma, C/EBPalpha, and genes marking terminal adipocyte differentiation, including Glut4, aP2, and fatty acid synthase. The mechanism underlying the effects of reduced SIRT2 in 3T3-L1 adipocytes includes increased acetylation of FOXO1, with direct interaction between SIRT2 and FOXO1. This interaction enhances insulin-stimulated phosphorylation of FOXO1, which in turn regulates FOXO1 nuclear and cytosolic localization. Thus, Sirt2 acts as an important regulator of adipocyte differentiation through modulation of FOXO1 acetylation/phosphorylation and activity and may play a role in controlling adipose tissue mass and function. 相似文献
84.
85.
86.
Previously, we have developed a genetically structured mathematical model to describe the inhibition of Escherichia coli lac operon gene expression by antigene oligos. Our model predicted that antigene oligos targeted to the operator region of the lac operon would have a significant inhibitory effect on beta-galactosidase production. In this investigation, the E. coli lac operon gene expression in the presence of antigene oligos was studied experimentally. A 21-mer oligo, which was designed to form a triplex with the operator, was found to be able to specifically inhibit beta-galactosidase production in a dose-dependent manner. In contrast to the 21-mer triplex-forming oligonucleotide (TFO), several control oligos showed no inhibitory effect. The ineffectiveness of the various control oligos, along with the fact that the 21-mer oligo has no homology sequence with lacZYA, and no mRNA is transcribed from the operator, suggests that the 21-mer oligo inhibits target gene expression by an antigene mechanism. To simulate the kinetics of lac operon gene expression in the presence of antigene oligos, a genetically structured kinetic model, which includes transport of oligo into the cell, growth of bacteria cells, and lac operon gene expression, was developed. Predictions of the kinetic model fit the experimental data quite well after adjustment of the value of the oligonucleotide transport rate constant (9.0 x 10(-)(3) min(-)(1)) and oligo binding affinity constant (1.05 x 10(6) M(-)(1)). Our values for these two adjusted parameters are in the range of reported literature values. 相似文献
87.
Brochier L Pontié Y Willson M Estrada-Mondaca S Czaplicki J Klaébé A Fournier D 《The Journal of biological chemistry》2001,276(21):18296-18302
Insect acetylcholinesterase (AChE), an enzyme whose catalytic site is located at the bottom of a gorge-like structure, hydrolyzes its substrate over a wide range of concentrations (from 2 microm to 300 mm). AChE is activated at low substrate concentrations and inhibited at high substrate concentrations. Several rival kinetic models have been developed to try to describe and explain this behavior. One of these models assumes that activation at low substrate concentrations partly results from an acceleration of deacetylation of the acetylated enzyme. To test this hypothesis, we used a monomethylcarbamoylated enzyme, which is considered equivalent to the acylated form of the enzyme and a non-hydrolyzable substrate analog, 4-oxo-N,N,N-trimethylpentanaminium iodide. It appears that this substrate analog increases the decarbamoylation rate by a factor of 2.2, suggesting that the substrate molecule bound at the activation site (K(d) = 130 +/- 47 microm) accelerates deacetylation. These two kinetic parameters are consistent with our analysis of the hydrolysis of the substrate. The location of the active site was investigated by in vitro mutagenesis. We found that this site is located at the rim of the active site gorge. Thus, substrate positioning at the rim of the gorge slows down the entrance of another substrate molecule into the active site gorge (Marcel, V., Estrada-Mondaca, S., Magné, F., Stojan, J., Klaébé, A., and Fournier, D. (2000) J. Biol. Chem. 275, 11603-11609) and also increases the deacylation step. This results in an acceleration of enzyme turnover. 相似文献
88.
89.
Quintero JM Molina R Fournier JM Benlloch M Ramos J 《Journal of experimental botany》2001,52(354):99-104
Excised 20-d-old sunflower roots (Helianthus annuus L. cv. Sun-Gro 393) were used to study the effect of different sugars on rubidium and water fluxes. The roots sensed and absorbed glucose from the external medium inducing the activation of rubidium accumulated in the root (Rb(+) root), the flux of exuded rubidium (J(Rb)) and, to a lesser degree, the exudation rate (J(v)). These effects were also triggered by fructose, but not by 6-deoxyglucose (6-dG), a glucose analogue which is not a substrate for hexokinase (HXK). The effect of 2-deoxyglucose (2-dG), an analogue that is phosphorylated but not further metabolized, was complex, suggesting an inhibitory effect on solute transport to the xylem. The amounts of glucose required to activate rubidium and water fluxes were similar to those previously reported to regulate different processes in other plants (0.5--10 mM). When sorbitol was used instead of glucose, neither rubidium uptake (Rb(+) root plus J(Rb)) nor J(v) was activated. It is proposed that glucose present in the root plays an important signalling role in the regulation of Rb(+) (K(+)) and water transport in plant roots. 相似文献
90.
Demart S Fournier JG Creminon C Frobert Y Lamoury F Marce D Lasmézas C Dormont D Grassi J Deslys JP 《Biochemical and biophysical research communications》1999,261(3):652-657
Loblolly pine (Pinus taeda L.) cell suspension cultures secrete monolignols when placed in 8% sucrose/20 mM KI solution, and these were used to identify phenylpropanoid pathway flux-modulating steps. When cells were provided with increasing amounts of either phenylalanine (Phe) or cinnamic acid, cellular concentrations of immediate downstream products (cinnamic and p-coumaric acids, respectively) increased, whereas caffeic and ferulic acid pool sizes were essentially unaffected. Increasing Phe concentrations resulted in increased amounts of p-coumaryl alcohol relative to coniferyl alcohol. However, exogenously supplied cinnamic, p-coumaric, caffeic, and ferulic acids resulted only in increases in their intercellular concentrations, but not that of downstream cinnamyl aldehydes and monolignols. Supplying p-coumaryl and coniferyl aldehydes up to 40, 000-320,000-fold above the detection limits resulted in rapid, quantitative conversion into the monolignols. Only at nonphysiological concentrations was transient accumulation of intracellular aldehydes observed. These results indicate that cinnamic and p-coumaric acid hydroxylations assume important regulatory positions in phenylpropanoid metabolism, whereas cinnamyl aldehyde reduction does not serve as a control point. 相似文献