全文获取类型
收费全文 | 8135篇 |
免费 | 682篇 |
国内免费 | 8篇 |
专业分类
8825篇 |
出版年
2023年 | 30篇 |
2022年 | 84篇 |
2021年 | 130篇 |
2020年 | 69篇 |
2019年 | 113篇 |
2018年 | 158篇 |
2017年 | 119篇 |
2016年 | 239篇 |
2015年 | 380篇 |
2014年 | 435篇 |
2013年 | 458篇 |
2012年 | 577篇 |
2011年 | 580篇 |
2010年 | 368篇 |
2009年 | 343篇 |
2008年 | 461篇 |
2007年 | 443篇 |
2006年 | 406篇 |
2005年 | 405篇 |
2004年 | 408篇 |
2003年 | 361篇 |
2002年 | 325篇 |
2001年 | 308篇 |
2000年 | 245篇 |
1999年 | 223篇 |
1998年 | 79篇 |
1997年 | 81篇 |
1996年 | 60篇 |
1995年 | 59篇 |
1994年 | 39篇 |
1993年 | 31篇 |
1992年 | 80篇 |
1991年 | 84篇 |
1990年 | 54篇 |
1989年 | 57篇 |
1988年 | 49篇 |
1987年 | 45篇 |
1986年 | 32篇 |
1985年 | 35篇 |
1984年 | 34篇 |
1982年 | 24篇 |
1979年 | 20篇 |
1978年 | 25篇 |
1977年 | 23篇 |
1976年 | 25篇 |
1975年 | 19篇 |
1974年 | 25篇 |
1973年 | 20篇 |
1971年 | 20篇 |
1970年 | 19篇 |
排序方式: 共有8825条查询结果,搜索用时 0 毫秒
11.
Intermolecular histone H4 interactions in core nucleosomes 总被引:1,自引:0,他引:1
Chicken histone H4, labeled at methionine-84 with 1-N-pyrenyliodoacetamide, has been incorporated into a nucleosome-like particle with core length DNA and unmodified histones H2A, H2B, and H3. These synthetic nucleosomes exhibit properties very similar to those displayed by native particles and those labeled with other fluors. The emission spectrum of the pyrene-labeled nucleosome was characteristic of excited dimer (excimer) fluorescence, indicating that the single pyrene groups on the two H4 molecules are in close proximity in the reconstituted particle. Histone H4 was also labeled randomly at lysines with a group that contains two pyrene moieties separated by 12 A at most. Incorporation of this histone into nucleosome-like particles provides an excimer standard which does not depend on intermolecular interactions. The properties of the pyrene-containing nucleosome were examined as a function of ionic strength. It was found that the H4-H4 pyrene excimer fluorescence exhibited a cooperative disruption centered at 0.1 M NaCl which preceded increases in accessibility and environment polarity revealed by other fluors attached at the same site. 相似文献
12.
Effect of platelet-activating factor on airway vascular permeability: possible mechanisms 总被引:10,自引:0,他引:10
Evans T. W.; Chung K. F.; Rogers D. F.; Barnes P. J. 《Journal of applied physiology》1987,63(2):479-484
We studied the effects of the potent inflammatory mediator, platelet-activating factor (PAF), on vascular permeability in airways (and other tissues) of guinea pigs by measuring extravasation of circulating Evans blue dye. PAF caused a dose-dependent increase in vascular permeability. At 1 ng/kg iv, PAF caused an increase in Evans blue extravasation of 220% (P less than 0.05) in the trachea, with the greatest effect at a dose of 100 ng/kg (858%; P less than 0.01). Histamine (150 micrograms/kg iv) caused a 320% increase over base line in the trachea and 200% in main bronchi; this effect was equivalent to that induced by 10 ng/kg PAF in the trachea and 1 ng/kg in main bronchi. The duration of effect of PAF was greatest in main bronchi (less than 10 min). Platelet depletion with a cytotoxic antibody, or the cyclooxygenase inhibitor, indomethacin, or the cyclooxygenase-lipoxygenase inhibitor, BW 7556, did not affect the vascular permeability response to PAF. The PAF-receptor antagonist, BN 52063, inhibited Evans blue extravasation in the airways in a dose-dependent manner, with complete inhibition at 5 mg/kg. Thus PAF-induced airway vascular leakage is mediated by specific receptors but not by products of arachidonic acid metabolism or by platelets. Increased airway microvascular leakage induced by PAF may lead to plasma extravasation and airway edema, factors that may contribute to the airway narrowing and hyperresponsiveness induced by PAF. 相似文献
13.
14.
Heart and liver mitochondrial, as well as liver peroxisomal, carnitine acetyltransferase was purified to apparent homogeneity and some properties, primarily of heart mitochondrial carnitine acetyltransferase, were determined. Hill coefficients for propionyl-CoA are 1.0 for each of the enzymes. The molecular weight of heart mitochondrial carnitine acetyltransferase, determined by SDS-PAGE, is 62,000. It is monomeric in the presence of catalytic amounts of substrate. Polyclonal antibodies against purified rat liver peroxisomal carnitine acetyltransferase precipitate liver and heart mitochondrial and liver peroxisomal carnitine acetyltransferase, but not liver peroxisomal carnitine octanoyltransferase. Liver peroxisomes, mitochondria, and microsomes and heart mitochondria all give multiple bands on Western blotting with the antibody against carnitine acetyltransferase. Major protein bands occur at the molecular weight of carnitine acetyltransferase and at 33 to 35 kDa. 相似文献
15.
Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases. 总被引:79,自引:0,他引:79
The macrolide rapamycin blocks cell cycle progression in yeast and various animal cells by an unknown mechanism. We demonstrate that rapamycin blocks the phosphorylation and activation of the 70 kd S6 protein kinases (pp70S6K) in a variety of animal cells. The structurally related drug FK506 had no effect on pp70S6K activation but at high concentrations reversed the rapamycin-induced block, confirming the requirement for the rapamycin and FK506 receptor, FKBP. Rapamycin also interfered with signaling by these S6 kinases, blocking serum-stimulated S6 phosphorylation and delaying entry of Swiss 3T3 cells into S phase. Neither rapamycin nor FK506 blocked activation of a distinct family of S6 kinases (RSKs) or the MAP kinases. These studies identify a rapamycin-sensitive signaling pathway, argue for a ubiquitous role for FKBPs in signal transduction, indicate that FK506-FKBP-calcineurin complexes do not interfere with pp70S6K signaling, and show that in fibroblasts pp70S6K, not RSK, is the physiological S6 kinase. 相似文献
16.
Inhibition of glutathione disulfide reductase by glutathione 总被引:2,自引:0,他引:2
Rat-liver glutathione disulfide reductase is significantly inhibited by physiological concentrations of the product, glutathione. GSH is a noncompetitive inhibitor against GSSG and an uncompetitive inhibitor against NADPH at saturating concentrations of the fixed substrate. In both cases, the inhibition by GSH is parabolic, consistent with the requirement for 2 eq. of GSH in the reverse reaction. The inhibition of GSSG reduction by physiological levels of the product, GSH, would result in a significantly more oxidizing intracellular environment than would be realized in the absence of inhibition. Considering inhibition by the high intracellular concentration of GSH, the steady-state concentration of GSSG required to maintain a basal glutathione peroxidase flux of 300 nmol/min/g in rat liver is estimated at 8-9 microM, about 1000-fold higher than the concentration of GSSG predicted from the equilibrium constant for glutathione reductase. The kinetic properties of glutathione reductase also provide a rationale for the increased glutathione (GSSG) efflux observed when cells are exposed to oxidative stress. The resulting decrease in intracellular GSH relieves the noncompetitive inhibition of glutathione reductase and results in an increased capacity (Vmax) and decreased Km for GSSG. 相似文献
17.
An endonuclease activity in human polymorphonuclear neutrophils that removes 8-hydroxyguanine residues from DNA+ 总被引:9,自引:0,他引:9
M H Chung H S Kim E Ohtsuka H Kasai F Yamamoto S Nishimura 《Biochemical and biophysical research communications》1991,178(3):1472-1478
An endonuclease that specifically removes 8-hydroxyguanine (oh8Gua) from DNA has been isolated from Escherichia coli. As the amount of oh8Gua produced in DNA of X-ray-irradiated mice is known to decrease with time after irradiation, an attempt was made to find a similar activity in human polymorphonuclear neutrophils (PMNs) using a synthetic dsDNA containing oh8Gua as a substrate. The PMN enzyme was isolated free of other DNases, and found to cleave the substrate DNA simultaneously at 2 sites, the phosphodiester bonds 5' and 3' to oh8Gua, producing free hydroxyl and phosphate groups, respectively. The enzyme showed almost no activity on DNAs containing other kinds of modified base tested or mismatched DNA. Thus human cells also contain an endonuclease that specifically removes oh8Gua residues from DNA. 相似文献
18.
19.
K. S. Chung 《Hydrobiologia》1981,78(2):177-181
The acclimation rates of temperature changes in Cyprinodon dearborni, collected from Laguna Los Patos, Cumana, Venezuela, were determined by the critical thermal maximum method.
At an increase in temperature (from 24 to 31°C) fish started to gain acclimation level after 3 hours and took 3 days to fully
get up to a higher level of resistance to heat death; however, at a decrease in temperature (from 3 t to 24°C) fish began
to lose its acclimation level after 12 days and required 39 days to reach a lower level of resistance to thermal death. 相似文献
20.