全文获取类型
收费全文 | 2056篇 |
免费 | 137篇 |
出版年
2021年 | 21篇 |
2020年 | 9篇 |
2019年 | 11篇 |
2018年 | 24篇 |
2017年 | 21篇 |
2016年 | 28篇 |
2015年 | 29篇 |
2014年 | 56篇 |
2013年 | 119篇 |
2012年 | 96篇 |
2011年 | 93篇 |
2010年 | 55篇 |
2009年 | 68篇 |
2008年 | 89篇 |
2007年 | 90篇 |
2006年 | 102篇 |
2005年 | 115篇 |
2004年 | 118篇 |
2003年 | 147篇 |
2002年 | 125篇 |
2001年 | 44篇 |
2000年 | 47篇 |
1999年 | 48篇 |
1998年 | 43篇 |
1997年 | 30篇 |
1996年 | 36篇 |
1995年 | 27篇 |
1994年 | 21篇 |
1993年 | 22篇 |
1992年 | 34篇 |
1991年 | 22篇 |
1990年 | 24篇 |
1989年 | 33篇 |
1988年 | 25篇 |
1987年 | 22篇 |
1986年 | 21篇 |
1985年 | 20篇 |
1984年 | 18篇 |
1983年 | 22篇 |
1982年 | 29篇 |
1981年 | 20篇 |
1980年 | 21篇 |
1979年 | 19篇 |
1978年 | 11篇 |
1977年 | 16篇 |
1976年 | 21篇 |
1975年 | 13篇 |
1974年 | 13篇 |
1973年 | 10篇 |
1972年 | 8篇 |
排序方式: 共有2193条查询结果,搜索用时 15 毫秒
11.
Tau proteins: the molecular structure and mode of binding on microtubules 总被引:29,自引:17,他引:12 下载免费PDF全文
Tau is a family of closely related proteins (55,000-62,000 mol wt) which are contained in the nerve cells and copolymerize with tubulin to induce the formation of microtubules in vitro. All information so far has indicated that tau is closely apposed to the microtubule lattice, and there was no indication of domains projecting from the microtubule polymer lattice. We have studied the molecular structure of the tau factor and its mode of binding on microtubules using the quick-freeze, deep-etch method (QF.DE) and low angle rotary shadowing technique. Phosphocellulose column-purified tubulin from porcine brain was polymerized with tau and the centrifuged pellets were processed by QF.DE. We observed periodic armlike elements (18.7 +/- 4.8 nm long) projecting from the microtubule surface. Most of the projections appeared to cross-link adjacent microtubules. We measured the longitudinal periodicity of tau projections on the microtubules and found it to match the 6-dimer pattern better than the 12-dimer pattern. The stoichiometry of tau versus tubulin in preparations of tau saturated microtubules was 1:approximately 5.0 (molar ratio). Tau molecules adsorbed on mica took on rodlike forms (56.1 +/- 14.1 nm long). Although both tau and MAP1 are contained in axons, competitive binding studies demonstrated that the binding sites of tau and MAP1A on the microtubule surfaces are most distinct, although they may partially overlap. 相似文献
12.
13.
The effect of eight different acetylcholinesterase inhibitors (AChEIs) on the activity of acetylcholinesterase (AChE) molecular forms was investigated. Aqueous-soluble and detergent-soluble AChE molecular forms were separated from rat brain homogenate by sucrose density sedimentation. The bulk of soluble AChE corresponds to globular tetrameric (G4), and monomeric (G1) forms. Heptylphysostigmine (HEP) and diisopropylfluorophosphate were more selective for the G1 than for the G4 form in aqueous-soluble extract. Neostigmine showed slightly more selectivity for the G1 form both in aqueous- and detergent-soluble extracts. Other drugs such as physostigmine, echothiophate, BW284C51, tetrahydroaminoacridine, and metrifonate inhibited both aqueous- and detergent-soluble AChE molecular forms with similar potency. Inhibition of aqueous-soluble AChE by HEP was highly competitive with Triton X-100 in a gradient, indicating that HEP may bind to a detergent-sensitive non-catalytic site of AChE. These results suggest a differential sensitivity among AChE molecular forms to inhibition by drugs through an allosteric mechanism. The application of these properties in developing AChEIs for treatment of Alzheimer disease is considered.Special issue dedicated to Dr. Morris H. Aprison. 相似文献
14.
15.
Summary (±)-Tricarbonyl 6-3-methylbenzyl alcohol)chromium was resolved to of 100%e.e. and of 92%e.e. by lipase-catalyzed transesterifications arranged in homotopic and heterotopic double resolutions. 相似文献
16.
17.
Oxygen radical-mediated lipid peroxidation and inhibition of Ca2+-ATPase activity of cardiac sarcoplasmic reticulum 总被引:2,自引:0,他引:2
R C Kukreja E Okabe G M Schrier M L Hess 《Archives of biochemistry and biophysics》1988,261(2):447-457
Oxygen radicals have been implicated as important mediators of myocardial ischemic and reperfusion injury. A major product of oxygen radical formation is the highly reactive hydroxyl radical via a biological Fenton reaction. The sarcoplasmic reticulum is one of the major target organelles injured by this process. Using a oxygen radical generating system consisting of dihydroxyfumarate and Fe3+-ADP, we studied lipid peroxidation and Ca2+-ATPase of cardiac sarcoplasmic reticulum. Incubation of sarcoplasmic reticulum with dihydroxyfumarate plus Fe3+-ADP significantly inhibited enzyme activity. Addition of superoxide dismutase, superoxide dismutase plus catalase (15 micrograms/ml) or iron chelator, deferoxamine (1.25-1000 microM) protected Ca2+-ATPase activity. Time course studies showed that this system inhibited enzyme activity in 7.5 to 10 min. Similar exposure of sarcoplasmic reticulum to dihydroxyfumarate plus Fe3+-ADP stimulated malondialdehyde formation. This effect was inhibited by superoxide dismutase, catalase, singlet oxygen, and hydroxyl radical scavengers. EPR spin-trapping with 5,5-dimethyl-1-pyrroline-N-oxide verified production of the hydroxyl radical. The combination of dihydroxyfumarate and Fe3+-ADP resulted in a spectrum of hydroxyl radical spin trap adduct, which was abolished by ethanol, catalase, mannitol, and superoxide dismutase. The results demonstrate the role of oxygen radicals in causing inactivation of Ca2+-ATPase and inhibition of lipid peroxidation of the sarcoplasmic reticulum which could possibly be one of the important mechanisms of oxygen radical-mediated myocardial injury. 相似文献
18.
Establishment of a Sensitized Immunoblotting Method for Measuring Plant Tubulin Content 总被引:1,自引:0,他引:1
A sensitized immunoblotting method was established for measuringsmall amounts of plant tubulin. The method involves electrophoretictransfer of protein including tubulin from SDS-polyacrylamidegels onto nitrocellulose paper, successive incubation of thenitrocellulose paper with a mouse monoclonal antibody to - orß-tubulin of chicken brain, an antibody to mouse IgGas the second antibody and the radioactive iodinated proteinA, and determination of the radioactivities of the bands onthe nitrocellulose paper thus probed. The radioactivities werelinearly proportional to the amounts of - or ß-tubulinfrom dark-grown Vigna mungo seedlings within a range of 4 to56 ng or of 4 to 32 ng, respectively. This method was used to estimate the tubulin contents of severalplant species using Vigna tubulin as a standard. -Tubulin contentsthus estimated were 25, 9, 19 and 11 µg-equivalents ofVigna tubulin per mg protein for Vigna seedlings, Daucus suspensioncells, Catharanthus suspension cells and Mougeolia cells, respectively.ß-Tubulin contents of Vigna, Daucus, Catharanthusand Mougeotia cells were 29, 10, 13 and 5 µg-equivalentsof Vigna tubulin per mg protein, respectively. (Received August 6, 1985; Accepted December 5, 1985) 相似文献
19.
Yuzuru Matsuda Nobuo Nakanishi Geneva Dickens Gordon Guroff 《Journal of neurochemistry》1986,47(6):1728-1734
Soluble extracts from nerve growth factor (NGF)-stimulated PC12 cells prepared by alkaline lysis show a two- to 10-fold greater ability to phosphorylate the 40S ribosomal protein S6 than do extracts from control cells. The alkaline lysis method yields a preparation of much higher specific activity than does sonication. Half-maximal incorporation of 32P from [32P]ATP into S6 occurred after 4-7 min of NGF treatment. The partially purified NGF-sensitive S6 kinase has a molecular weight of 45,000. It is not inhibited by NaCl, chlorpromazine, or the specific inhibitor of cyclic AMP (cAMP)-dependent protein kinase, nor is it activated by addition of diolein plus phosphatidylserine. Trypsin treatment of either crude extracts or partially purified S6 kinase from control or NGF-treated cells was without effect. These data suggest that the S6 kinase stimulated by NGF is neither cAMP-dependent protein kinase or protein kinase C nor the result of tryptic activation of an inactive proenzyme. Treatment of intact cells with dibutyryl cAMP or 5'-N-ethylcarboxamideadenosine also increases the subsequent cell-free phosphorylation of S6. This observation suggests that cAMP-dependent protein kinase may be involved in the phosphorylation of S6 kinase. 相似文献
20.
Yutaka Suzuki Yoshiteru Harada Akinori Ueno Makoto Katori Haruya Okabe 《Prostaglandins & other lipid mediators》1986,32(3)
Filling of the gastric lumen of rats with 1.0 M NaCl solution (5 ml) for 10 min under urethane anesthesia caused an increase in the gastric fluid concentrations of prostaglandin (PG) E2, 13, 14-dihydro-15-keto-PGE2 and 6-keto-PGF1α as determined by radioimmunoassay. PGE2 was the major PG generated. The levels of PGE2 in the gastric fluid were increased dose-dependently after filling the lumen with 0.3, 0.5, 0.7 or 1.0 M NaCl solutions. The pH of the gastric fluid increased similarly after 0.5 to 1.0 M NaCl solutions. Indomethacin (10 mg/kg, i.p.) suppressed the PGE2 increase caused by 1.0 M NaCl solution, but did not prevent the increase of the pH of the gastric fluid induced by intragastric 1.0 M NaCl. Infusion of tetragastrin (62.5 μg/kg/hr, i.v., for 10 min) caused a marked increase of acid secretion without modifying intragastic concentration of PGE2. The acid secretion due to tetragastrin was completely inhibited after intragastric administration of 1.0 M NaCl solution, while indomethacin restored the tetragastrin-induced acid secretion, with prevention of a rise of intragastric PGE2 levels. These observations suggest that 1.0 M NaCl solutions suppress basal intragastric acid through a mechanism which is independent of prostaglandins. In contrast, the suppression of tetragastrin-induced acid secretion by intragastric 1.0 M NaCl solution appears to be mediated through a release of prostaglandins 相似文献