全文获取类型
收费全文 | 8257篇 |
免费 | 457篇 |
国内免费 | 494篇 |
出版年
2023年 | 101篇 |
2022年 | 127篇 |
2021年 | 210篇 |
2020年 | 210篇 |
2019年 | 260篇 |
2018年 | 270篇 |
2017年 | 187篇 |
2016年 | 183篇 |
2015年 | 255篇 |
2014年 | 410篇 |
2013年 | 641篇 |
2012年 | 362篇 |
2011年 | 433篇 |
2010年 | 357篇 |
2009年 | 409篇 |
2008年 | 398篇 |
2007年 | 411篇 |
2006年 | 369篇 |
2005年 | 314篇 |
2004年 | 294篇 |
2003年 | 282篇 |
2002年 | 241篇 |
2001年 | 157篇 |
2000年 | 154篇 |
1999年 | 174篇 |
1998年 | 169篇 |
1997年 | 144篇 |
1996年 | 114篇 |
1995年 | 114篇 |
1994年 | 107篇 |
1993年 | 98篇 |
1992年 | 114篇 |
1991年 | 93篇 |
1990年 | 92篇 |
1989年 | 79篇 |
1988年 | 80篇 |
1987年 | 75篇 |
1986年 | 68篇 |
1985年 | 103篇 |
1984年 | 94篇 |
1983年 | 74篇 |
1982年 | 72篇 |
1981年 | 55篇 |
1980年 | 64篇 |
1979年 | 36篇 |
1978年 | 33篇 |
1977年 | 28篇 |
1976年 | 25篇 |
1975年 | 22篇 |
1974年 | 23篇 |
排序方式: 共有9208条查询结果,搜索用时 15 毫秒
91.
Inositol Phospholipid Hydrolysis in Rat Cerebral Cortical Slices: I. Receptor Characterisation 总被引:35,自引:17,他引:18
Characterisation of receptor-mediated breakdown of inositol phospholipids in rat cortical slices has been performed using a direct assay which involves prelabelling with [3H]inositol. When slices were preincubated with [3H]inositol, lithium was found to greatly amplify the capacity of receptor agonists such as carbachol, noradrenaline, and 5-hydroxytryptamine to increase the amount of radioactivity appearing in the inositol phosphates. Using a large variety of agonists and antagonists it could be shown that cholinergic muscarinic, alpha 1-adrenoceptor, and histamine H1 receptors appear to be linked to inositol phospholipid breakdown in cortex. The large responses produced by receptor agonists allowed a clear discrimination between full and partial agonists as well as quantitative analysis of competitive antagonists for each receptor. Whereas carbachol and acetylcholine (in the presence of a cholinesterase inhibitor) were full agonists, oxotremorine and arecoline were only partial agonists. Very low concentrations of atropine shifted the carbachol dose-response curve to the right and allowed inhibition constants for the antagonist to be easily calculated. The nicotinic antagonist, mecamylamine, was ineffective. Noradrenaline adrenaline were full agonists at alpha 1-adrenoceptors, but phenylephrine and probably methoxamine were partial agonists. Prazosin, but not yohimbine, potently and competitively antagonised the noradrenaline inositol phospholipid response. Mepyramine but not cimetidine competitively antagonised the histamine response. These data provide strong confirmation for the potentiating effect of lithium on neurotransmitter inositol phospholipid breakdown and emphasise the ease with which functional responses at a number of cortical receptors can be characterised. 相似文献
92.
Presynaptic Nicotinic Cholinergic Receptors Labeled by [3 H]Acetylcholine on Catecholamine and Serotonin Axons in Brain 总被引:5,自引:0,他引:5
Nicotinic cholinergic receptor binding sites labeled by [3H]acetylcholine were measured in the cerebral cortices, thalami, striata, and hypothalami of rats lesioned by intraventricular injection of either 6-hydroxydopamine or 5, 7-dihydroxytryptamine. In addition, [3H]acetylcholine binding sites were measured in the cerebral cortices of rats lesioned by injection of ibotenic acid into the nucleus basalis magnocellularis. [3H]Acetylcholine binding was significantly decreased in the striata and hypothalami of both 6-hydroxydopamine- and 5,7-dihydroxytryptamine-lesioned rats. There was no change in binding in the cortex or thalamus by either lesion. Ibotenic acid lesions of the nucleus basalis magnocellularis, which projects cholinergic axons to the cortex, did not alter [3H]acetylcholine binding. These results provide evidence for a presynaptic location of nicotinic cholinergic binding sites on catecholamine and serotonin axons in the striatum and hypothalamus. 相似文献
93.
Richard B. Rothman Uwe K. Schumacher Candace B. Pert 《Journal of neurochemistry》1984,43(4):1197-1199
Abstract: (β-FNA, the β -fumaramate methyl ester of naltrexone, has been shown to antagonize irreversibly the actions of morphine on the guinea pig ileum and mouse vas deferens bioassays but does not affect the actions of δ-receptor ligands on the mouse vas deferens bioassay, suggesting that the compound does not irreversibly bind to the S receptor. In this paper we examine the effect of (β -FNA on the binding of the prototypic δ agonists, Leuenkephalin and d -Ala2 - d -Leu5 -enkephalin, its metabolically stable analogue, and show that treatment of membranes with β -FNA does lead to alterations in the in vitro properties of δ receptors. 相似文献
94.
Effect of Phospholipase Digestion and Lysophosphatidylcholine on Dopamine Receptor Binding 总被引:4,自引:4,他引:0
[3H]Spiperone specific binding by microsomal membranes isolated from sheep caudate nucleus is decreased by trypsin and phospholipase A2 (Vipera russeli), but is insensitive to neuraminidase. The inhibitory effect of phospholipase A2 is correlated with phospholipid hydrolysis. After 15 min of phospholipase (5 micrograms/mg protein) treatment, a maximal effect is observed; the maximal lipid hydrolysis is about 56% and produces 82% reduction in [3H]spiperone binding. Equilibrium binding studies in nontreated and treated membranes showed a reduction in Bmax from a value of 388 +/- 9.2 fmol/mg protein before phospholipase treatment to a value of 52 +/- 7.8 fmol/mg protein after treatment, but no change in affinity (KD = 0.24 +/- 0.042 nM) was observed. Albumin washing of treated membranes removes 47% of lysophosphatidylcholine produced by phospholipid hydrolysis without recovering [3H]spiperone binding activity. However, the presence of 2.5% albumin during phospholipase A2 action (1.5 micrograms/mg protein) prevents the inhibitory effect of phospholipase on [3H]spiperone binding to the membranes, although 28% of the total membrane phospholipid is hydrolysed. Lysophosphatidylcholine, a product of phospholipid hydrolysis, mimics the phospholipase A2 effect on receptor activity, but the [3H]spiperone binding inhibition can be reversed by washing with 2.5% defatted serum albumin. Addition of microsomal lipids to microsomal membranes pretreated with phospholipase does not restore [3H]spiperone stereospecific binding. It is concluded that the phospholipase-mediated inhibition of [3H]spiperone binding activity results not only from hydrolysis of membrane phospholipids, but also from an alteration of the lipid environment by the end products of phospholipid hydrolysis. 相似文献
95.
Charles G. Crispens Philip S. Porter John R. J. Sorenson 《Biological trace element research》1986,10(1):19-24
Plasma copper and zinc levels were measured in SJL/J mice, an inbred strain characterized by a high, spontaneous incidence
of reticulum cell sarcoma (RCS). The changes with age in mean concentrations of these metals were consistent with a physiological
response that is required for remission of neoplasia. Treatment of SJL/J mice with a copper complex, Cu(II)(3,4-diisopropylsalicylate)2 (Cu 3,5-DIPS), dissolved in a 10% Tween 80-saline solution revealed a decrease in survival and decline in the incidence of
RCS at 52 wk of age. The toxic effects of Cu 3,5-DIPS therapy appeared to be related to the intraperitoneal route of administration
and to extracellular deposition of collagen. The inhibitory effect on tumor development was not related to Cu 3,5-DIPS. Rather,
Tween 80 was found to be the factor of importance. 相似文献
96.
97.
An advantage of aprotic polar solvent systems in the study of monomer interactions relevant to the macromolecular state is demonstrated with the measurement of nucleoside amino proton exchange rates in DMSO/water mixtures. The DMSO/water solvent provides the first unequivocal observation of general acid catalysis of nucleic acid amino proton exchange, which is undetectable in aqueous solution due to the formation of the endocyclic protonated nucleobase. Suppression of nucleobase protonation in the presence of buffer acid is a consequence of anion desolvation in the aprotic solvent. The detected route of general acid catalysis is demonstrated as a consequence of Watson-Crick H-bonding, leading to the implication that amino chemistry is modulated in the helical state to decrease amino proton lifetime in the closed macromolecular context of conformational information obtained by hydrogen exchange methods. This useful property of the aprotic solvent can be extended to monomeric studies pertaining to specific local site interactions affecting the function and conformation of proteins and nucleic acids. 相似文献
98.
Summary H1° histones were purified by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis from human lung carcinoma (line DMS79), human hepatoblastoma (HepG2), human adult lung and human adult and fetal liver. The purified human H1° histones were analyzed for their amino acid composition and terminal residues. The comparative analysis of the amino acid compositions of the different human H1° histones showed that: (a) all the H1° preparations have the characteristically high lysine content associated with a low arginine content, which distinguishes outer histones from core histones; (b) H1° is distinguishable from other H1 histones by the presence of methionine and histidine; (c) H1° histones from human adult, fetal and cancer cells are very similar in amino acid composition, and in cancer cells the level of the H1° histone is not inversely related with cell growth rate nor with the expression of the -fetoprotein gene. 相似文献
99.
In cell suspensions of Pseudomonas carboxydovorans pulsed with lithotrophic substrates (CO or H2) in the presence of oxygen, formation of reduced pyridine nucleotides and of ATP could be demonstrated using the bioluminescent assay. Experiments employing base-acid transition, an uncoupler and inhibitors of ATPase or electron transport enabled us to propose a model for the formation of NAD(P)H in chemolithotrophically growing P. carboxydovorans.The protonophor FCCP (carbonly-p-trifluormethoxyphenylhydrazon) inhibited both, formation of NAD(P)H and of ATP. In the absence of oxygen, a chemical potential imposed by base-acid transition resulted in the formation of NAD(P)H and ATP when electrogenic substrates (CO or H2) were present. This suggests proton motive force-driven NAD(P)H formation. The proton motive force was generated by oxidation of substrate, and not by ATP hydrolysis, as obvious from NAD(P)H formation during inhibition of ATP synthesis by oligomycin and N,N-dicyclohexylcarbodiimide.That the CO-born electrons are transferred via the ubiquinone 10-cytochrome b region to NADH dehydrogenase functioning in the reverse direction, was indicated by inhibition of NAD(P)H formation by HQNO (2-n-heptyl-4-hydroxyquinoline-N-oxide) and rotenone, and by resistance to antimycin A.We conclude that in P. carboxydovorans, growing with CO or H2, electrons and a proton motive force, generated by respiration, are required to drive an reverse electron transfer for the formation of reduced pyridine nucleotides.Abbreviations CODH
carbon monoxide dehydrogenase
- DCCD
N,N-dicyclohexylcarbodiimide
- FCCP
carbonyl-p-trifluormethoxyphenylhydrazon
- HQNO
2-n-heptyl-4-hydroxyquinoline-N-oxide
- pmf
proton motive force 相似文献
100.
A general method for the synthesis of azido-ubiquinone derivatives has been developed directly by substituting one hydrogen atom on the benzoquinone ring with an azido group under weakly acidic conditions. The reaction takes several hours and the yield is generally low. The azido-ubiquinone was purified by preparative thin layer chromatography, and identified by NMR, IR and mass spectra. All the synthesized azido-ubiquinone derivatives show partial activity in mediating biological electron transfer in the dark, and show partial or complete inhibition upon photolysis. 相似文献