全文获取类型
收费全文 | 7994篇 |
免费 | 827篇 |
国内免费 | 5篇 |
出版年
2022年 | 59篇 |
2021年 | 67篇 |
2019年 | 58篇 |
2018年 | 80篇 |
2017年 | 58篇 |
2016年 | 139篇 |
2015年 | 218篇 |
2014年 | 263篇 |
2013年 | 350篇 |
2012年 | 439篇 |
2011年 | 410篇 |
2010年 | 305篇 |
2009年 | 281篇 |
2008年 | 463篇 |
2007年 | 466篇 |
2006年 | 409篇 |
2005年 | 424篇 |
2004年 | 434篇 |
2003年 | 449篇 |
2002年 | 375篇 |
2001年 | 142篇 |
2000年 | 109篇 |
1999年 | 120篇 |
1998年 | 121篇 |
1997年 | 79篇 |
1996年 | 91篇 |
1995年 | 76篇 |
1994年 | 95篇 |
1993年 | 92篇 |
1992年 | 100篇 |
1991年 | 84篇 |
1990年 | 85篇 |
1989年 | 80篇 |
1988年 | 71篇 |
1987年 | 77篇 |
1986年 | 90篇 |
1985年 | 99篇 |
1984年 | 97篇 |
1983年 | 87篇 |
1982年 | 89篇 |
1981年 | 79篇 |
1980年 | 76篇 |
1979年 | 82篇 |
1978年 | 65篇 |
1977年 | 65篇 |
1976年 | 56篇 |
1975年 | 52篇 |
1974年 | 67篇 |
1973年 | 52篇 |
1972年 | 46篇 |
排序方式: 共有8826条查询结果,搜索用时 15 毫秒
121.
The contribution of drug metabolites to cyproheptadine (CPH)-induced alterations in endocrine pancreatic -cells was investigated by examining the inhibitory activity of CPH and its biotransformation products, desmethylcyproheptadine (DMCPH), CPH-epoxide and DMCPH-epoxide, on hormone biosynthesis and secretion in pancreatic islets isolated from 50-day-old rats. Measurement of (pro)insulin (proinsulin and insulin) synthesis using incorporation of 3H-leucine showed that DMCPH-epoxide, DMCPH and CPH-epoxide were 22, 10 and 4 times, respectively, more potent than CPH in inhibiting hormone synthesis. The biosynthesis of (pro)insulin was also inhibited by CPH and DMCPH-epoxide in islets isolated from 21-day-old rat fetuses. The inhibitory action of CPH and its metabolites was apparently specific for (pro)insulin, and the synthesis of other islet proteins was not affected. Other experiments showed the metabolites of CPH were active in inhibiting glucose-stimulated insulin secretion but were less potent than the parent drug in producing this effect. CPH and its structurally related metabolites, therefore, have differential inhibitory activities on insulin synthesis and release. The observation that CPH metabolites have higher potency than CPH to inhibit (pro)insulin synthesis, when considered with published reports on the disposition of the drug in rats, indicate that CPH metabolites, particularly DMCPH-epoxide, are primarily responsible for the insulin depletion observed when the parent compound is given to fetal and adult animals.Abbreviations CPH
cyproheptadine
- CPH-epoxide
cyproheptadine-10-11-epoxide
- DMCPH
desmethylcyproheptadine
- DMCPH-epoxide
desmethylcyproheptadine-10,11-epoxide
- HPLC
high-performance liquid chromatography
- KBB
Krebs biocarbonate buffer
Recipient of a Society of Toxicology Predoctoral Research Fellowship.Present address: Department of Biochemistry, The University of Hong Kong, Hong Kong. 相似文献
122.
123.
Lawrence W. Fitzgerald‡ Lynne Kaplinsky† Harold K. Kimelberg†‡ 《Journal of neurochemistry》1990,55(6):2008-2014
The oxidative deamination of serotonin (5-HT) to 5-hydroxyindoleacetic acid (5-HIAA) by rat primary astrocyte cultures was investigated in intact cells using HPLC. All detectable 5-HIAA accumulated in the extracellular medium, and its rate of production was proportional to the 5-HT concentration over the tested range of 5 x 10(-7) to 10(-4) M. At 5 x 10(-7) M 5-HT, intracellular 5-HT was detectable only in astrocytes treated with monoamine oxidase (MAO) inhibitors. These findings are consistent with the idea that 5-HT taken up into astrocytes is not stored for re-release, but is rapidly metabolized to 5-HIAA, which is then extruded from the cell. At 5 x 10(-7) M 5-HT, 5-HIAA formation in intact cells was blocked 63% by the selective high-affinity 5-HT uptake inhibitor fluoxetine. 5-HT oxidation to 5-HIAA is carried out principally by MAO-A, because clorgyline was more effective at inhibiting the production of 5-HIAA than was pargyline. Radioenzymatic determinations of MAO activity in cell homogenates supported these findings, because under these conditions clorgyline was 1,000-fold more effective than pargyline at inhibiting MAO activity toward 14C-labelled 5-HT. However, the relatively selective MAO-B substrate beta-phenylethylamine (PEA) was also oxidized, showing that these cultures also contained MAO-B activity; the Km values for MAO-A oxidation of 5-HT and MAO-B oxidation of PEA were 135 and 45 microM, and Vmax values were 88 and 91 nmol/mg of total cell protein/h, respectively. Higher concentrations of PEA (greater than 20 microM) were oxidized by both MAO-A and MAO-B isozymes.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
124.
125.
126.
Summing-up of strategies for tick-borne disease control in Africa, especially east Africa 总被引:1,自引:0,他引:1
J A Lawrence 《Parassitologia》1990,32(1):113-115
127.
Down''s Syndrome Individuals Begin Life with Normal Levels of Brain Cholinergic Markers 总被引:3,自引:1,他引:2
Stephen Kish Harry Karlinsky Lawrence Becker Joseph Gilbert Michelle Rebbetoy Li-Jan Chang Linda DiStefano Oleh Hornykiewicz 《Journal of neurochemistry》1989,52(4):1183-1187
We measured the activities of the cholinergic marker enzymes choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in autopsied brains of seven infants (age range 3 months to 1 year) with Down's syndrome (DS), a disorder in which virtually all individuals will develop by middle age the neuropathological changes of Alzheimer's disease accompanied by a marked brain cholinergic reduction. When compared with age-matched controls cholinergic enzyme activity was normal in all brain regions of the individuals with infant DS with the exception of above-normal activity in the putamen (ChAT) and the occipital cortex (AChE). Our neurochemical observations suggest that DS individuals begin life with a normal complement of brain cholinergic neurons. This opens the possibility of early therapeutic intervention to prevent the development of brain cholinergic changes in patients with DS. 相似文献
128.
M Rodriguez P Moreau M Paulik J Lawrence D J Morré D Morré 《Biochimica et biophysica acta》1992,1107(1):131-138
This report concerns development of a cell-free system from rat liver to study transport of membrane constituents from the Golgi apparatus to the plasma membrane. Highly purified Golgi apparatus as donor and a mixture of sheets and vesicles as plasma membrane acceptor fractions were combined to analyze requirements for lipid and protein transport. In the reconstituted system, the Golgi apparatus donor was in suspension. To measure transfer, membrane constituents of the donor membranes were radiolabeled with [3H]acetate (lipids) or [3H]leucine (proteins). The plasma membrane vesicles were used as the acceptor and were unlabeled and immobilized on nitrocellulose for ease of recovery and analysis. The reconstituted cell-free transfer was dependent on temperature, but even at 37 degrees C, the amount of transfer did not increase with added ATP, was not specific for any particular membrane fraction or subfraction nor was it facilitated by cytosol. ATP was without effect both in the presence or absence of a cytosolic fraction capable of the support of cell-free transfer in other systems. In contrast to results with ATP, NADH added to the reconstituted system resulted in an increased amount of transfer. A further increase in transfer was obtained with NADH plus a mixture of ascorbate and dehydroascorbate to generate ascorbate free radical. The transfer of labeled membrane constituents from the Golgi apparatus to the plasma membrane supported by NADH plus ascorbate radical was stimulated by a cytosol fraction enriched in less than 10 kDa components. This was without effect in the absence of NADH/ascorbate radical or with ATP as the energy source. Specific transfer was inhibited by both N-ethylmaleimide and GTP gamma S. The findings point to the possibility of redox activities associated with the trans region of the Golgi apparatus as potentially involved in the transport of membrane vesicles from the Golgi apparatus to the cytoplasmic surface of the plasma membrane. 相似文献
129.
The three-dimensional structure of the seed storage protein phaseolin at 3 A resolution. 总被引:4,自引:0,他引:4
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M C Lawrence E Suzuki J N Varghese P C Davis A Van Donkelaar P A Tulloch P M Colman 《The EMBO journal》1990,9(1):9-15
The polypeptides of the trimeric seed storage protein phaseolin comprise two structurally similar units each made up of a beta-barrel and an alpha-helical domain. The beta-barrel has the 'jelly-roll' folding topology of the viral coat proteins and the alpha-helical domain shows structural similarity to the helix-turn-helix motif found in certain DNA-binding proteins. 相似文献
130.
Amphipathic helices, which play important roles in protein structure,occur in a wide variety of lengths. Yet existing methods employfixed window lengths. We present a hierarchical procedure thatidentifies the Q most significant amphipathic helices regardlessof length. Since the observed hydrophobicities are not normallydistributed, test statistics usually employed for least-squaresregression are inappropriate for assessing statistical significanceof amphipathic helices. We show that an adjusted F statisticprovides a good test. An application to the envelope proteinof HIV finds an unexpected long amphipathic helix in gp41.
Received on July 12, 1989; accepted on February 28, 1990 相似文献