全文获取类型
收费全文 | 694225篇 |
免费 | 70533篇 |
国内免费 | 377篇 |
专业分类
765135篇 |
出版年
2018年 | 7215篇 |
2017年 | 7020篇 |
2016年 | 9340篇 |
2015年 | 11122篇 |
2014年 | 13650篇 |
2013年 | 19733篇 |
2012年 | 22296篇 |
2011年 | 22984篇 |
2010年 | 15711篇 |
2009年 | 14223篇 |
2008年 | 20246篇 |
2007年 | 20960篇 |
2006年 | 19730篇 |
2005年 | 18886篇 |
2004年 | 18726篇 |
2003年 | 17976篇 |
2002年 | 17443篇 |
2001年 | 34320篇 |
2000年 | 34137篇 |
1999年 | 26535篇 |
1998年 | 8276篇 |
1997年 | 8721篇 |
1996年 | 8059篇 |
1995年 | 7427篇 |
1994年 | 7153篇 |
1993年 | 7080篇 |
1992年 | 20855篇 |
1991年 | 20255篇 |
1990年 | 19617篇 |
1989年 | 19273篇 |
1988年 | 17630篇 |
1987年 | 16474篇 |
1986年 | 15286篇 |
1985年 | 15209篇 |
1984年 | 12377篇 |
1983年 | 10362篇 |
1982年 | 7540篇 |
1981年 | 6694篇 |
1980年 | 6429篇 |
1979年 | 11467篇 |
1978年 | 8777篇 |
1977年 | 8070篇 |
1976年 | 7482篇 |
1975年 | 8463篇 |
1974年 | 9184篇 |
1973年 | 8972篇 |
1972年 | 8116篇 |
1971年 | 7454篇 |
1970年 | 6457篇 |
1969年 | 6191篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
Protein metal-binding sites. 总被引:2,自引:0,他引:2
Metal ions have a role in a variety of important functions in proteins including protein folding, assembly, stability, conformational change, and catalysis. The presence or absence of a given metal ion is crucial to the conformation or activity of over one third of all proteins. Recent developments have been made in the understanding and design of metal-binding sites in proteins, an important and rapidly advancing area of protein engineering. 相似文献
82.
Maleylated-BSA suppresses IFN-gamma-mediated Ia expression in murine peritoneal macrophages 总被引:1,自引:0,他引:1
T A Hamilton P V Gainey D O Adams 《Journal of immunology (Baltimore, Md. : 1950)》1987,138(12):4063-4068
Maleylated bovine serum albumin (maleyl-BSA) and other polyanionic polymers that are recognized by cell surface receptors on macrophages have been shown to induce chemotaxis, protease secretion, and tumoricidal function in this cell type. In this paper the effect of maleyl-BSA on Ia antigen expression has been evaluated. In a fashion similar to LPS, maleyl-BSA suppressed IFN-gamma-induced expression of Ia in a time- and dose-dependent manner. Also like LPS, maleyl-BSA stimulated the production and secretion of substantial amounts of PGE2 over a 24-hr period. This did not, however, appear to be the primary mechanism by which expression of Ia was suppressed, because co-treatment of the cells with indomethacin, which totally inhibited the production of PGE2, only minimally affected the suppressive activity. Surprisingly, the suppressive activity of both maleyl-BSA and LPS could be largely abrogated by co-treatment of the cells with cyclohexamide during the time period when Ia expression was sensitive to suppression. This effect was selective in that PGE2- or dibutyryl cyclic AMP-induced suppression of Ia expression was not affected by cyclohexamide treatment. The data support the concept that there are multiple molecular mechanisms involved in the negative regulation of IFN-gamma-induced Ia expression in macrophages. Such mechanisms may include, in addition to the synthesis of PGE2 and consequent elevation in intracellular levels of cyclic AMP, one or more proteins made early after treatment with either maleyl-BSA or LPS. Thus the function of some of these early gene products may be to regulate expression of functional genes such as that encoding Ia antigen. 相似文献
83.
V K Khugaeva E D Klimenko P N Aleksandrov G F Leskova M I Reutov 《Biulleten' eksperimental'no? biologii i meditsiny》1985,100(7):15-19
Experiments were made on rabbit fed an atherogenic diet (0.5 g/kg cholesterol) singly for 15 and 24 h and repeatedly for 3, 9 and 30 days. At early stages of lipid metabolism distress the interrelationship was established between blood rheological disorders and microcirculatory abnormalities. The dependence of the initial reaction of some rheological characteristics on their initial level was marked. 相似文献
84.
M A Pass M W Goosem S Pollitt 《Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol.》1985,82(2):457-461
The metabolism of the cholestatic triterpene acid reduced lantadene A has been studied in susceptible and resistant rats and in sheep which are susceptible to intoxication. Sheep and susceptible female rats produced a similar major metabolite and rats produced a second metabolite which was a glucuronide. These metabolites were also observed in extracts of bile canalicular membranes prepared from intoxicated rats. Resistant male and female rats produced a similar major metabolite which was different to those synthesized by susceptible animals. It is concluded that in rats and sheep there is a correlation between the type of metabolites produced in the liver and the susceptibility to intoxication by reduced lantadene A. 相似文献
85.
Transport of chloride across cell membranes through exchange, cotransport, or conductive pathways is a subject of great biological importance. Current methods of measurement are restricted in their sensitivity, time resolution, and applicability. A new transport measurement technique has been developed on the basis of the fluorescence quenching by chloride of the dye 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ). SPQ fluorescence quenching by chloride is rapid (less than 1 ms) and sensitive, with a greater than 50% decrease in fluorescence at 10 mM chloride. SPQ fluorescence is not altered by other physiological anions or by pH and can be used to measure both neutral and conductive transport processes. The high water solubility and membrane permeability properties of SPQ make it ideal for use in both membrane vesicles and cells. Chloride transport determined with SPQ was validated by measurement of erythrocyte chloride/anion exchange and membrane vesicle chloride conductance. 相似文献
86.
Purification and characterization of a membrane-bound protein kinase from spinach thylakoids 总被引:3,自引:0,他引:3
A protein kinase was isolated from spinach thylakoid membranes by solubilization with octyl glucoside and cholate. The enzyme was purified to apparent homogeneity by ammonium sulfate precipitation, gel filtration, and sucrose density centrifugation, followed by affinity chromatography on either Affi-Gel blue (yielding denatured enzyme) or on histone cross-linked to Sepharose (yielding active enzyme). Electrophoresis on denaturing polyacrylamide gels, followed by staining with silver, revealed the kinase as a single band corresponding to an apparent molecular mass of 64 kDa. The active enzyme underwent autophosphorylation and could be detected by autoradiography following incubation with [gamma-32P]ATP and Mg2+ ion. The specific phosphotransferase activity of purified kinase was approximately 30 nmol of phosphate min-1 (mg protein)-1 with lysine-rich histone (III-S or V-S) as substrate; casein was phosphorylated at approximately 30% of this rate. The physiological substrate for the kinase is presumed to be light-harvesting chlorophyll a/b protein complex. In solubilized form, this was phosphorylated at approximately 10% of the rate observed with histone III-S as substrate, or 10-100 times slower than the estimated rate of phosphorylation of the light-harvesting complex in situ. Possible reasons for this shortfall are considered. The kinase is proposed as the principal effector of thylakoid protein phosphorylation and associated State transition phenomena. 相似文献
87.
(+)-2,9 alpha-Dimethyl-5-(m-hydroxyphenyl)morphan is the only phenylmorphan analog whose affinity for opioid kappa-receptors is greater than its affinity for opioid mu-receptors. Pharmacologically, the compound is a pure opioid antagonist devoid of agonist activity in in vivo assays of antinociception. The absolute configuration of the compound has been determined to be (1R,5S,9R) from an X-ray crystallographic study of the chloride salt. Thus, the absolute configuration corresponds to that of the atypical opioid agonist (-)-phenylmorphan while the weak atypical agonist (-)-2,9 alpha-dimethyl-5-(m- hydroxyphenyl)morphan corresponds to the potent morphine-like (+)-phenylmorphan. The preferred orientations of the phenyl ring for the two stereoisomers were determined using the molecular mechanics program MM2-87 and found to vary from that of the two parent compounds. The atypical properties of the two 9 alpha-methyl analogs is consistent with an opioid ligand model which proposes that morphine-like properties require a particular range of phenyl orientations. There was good agreement between the structure obtained from X-ray crystallography and computed with the MM2-87 program. 相似文献
88.
V A Frolov G Mall P Rieger Kh Derks Z Antoni 《Biulleten' eksperimental'no? biologii i meditsiny》1987,104(12):739-741
Intensive synthesis of collagen-like substance was revealed in the rabbit myocardium during experimental diphtheria intoxication. It was more marked in the right ventricle 24 hours after the injection of diphtheria toxin. Since similar changes (the substance was mainly formed around blood vessels) have been observed in other cases of toxic myocardial alterations (i.e. ethanol intoxication, injection of pharmacological agents, etc.), it can be assumed that it is a standard protective reaction of the altered heart to the penetration of toxic agents from the blood into the myocardial tissue. 相似文献
89.
EEG activity was recorded in rats submitted to osmotic opening of the BBB by intracarotid mannitol infusion.This procedure produced an immediate short-lasting depression of the EEG and a tardive paroxysmal EEG activity. Both these phenomena were more relevant on the ipsilateral hemisphere. In some instances a tonico-clonic seizure was recorded.Pre-treatment with diazepam abolished the occurrence of the tardive EEG and behavioral modifications.In accord with previous findings, focal seizure activity is likely to be responsible for the metabolic abnormalities associated with osmotic opening of the BBB. This preparation therefore produces in the brain unphysiological states in respect to local metabolism and electrical function. 相似文献
90.
N. V. Ozolina E. V. Kolesnikova V. N. Nurminsky I. S. Nesterkina L. V. Dudareva L. I. Donskaya R. K. Salyaev 《Biochemistry (Moscow) Supplemental Series A: Membrane and Cell Biology》2010,4(3):297-301
The changes in transport activity of tonoplast proton pumps under the influence of exogenous NO donator and modulation of
Ca2+ concentration jointly and separately were investigated at different stages of ontogenesis and under hyperosmotic stress.
The results suggest that both exogenous NO donator and Ca2+ ions can influence the activity of transport processes related to tonoplast and this influence is especially evident in the
period of growth and accumulation of metabolites. Under hyperosmotic stress, H+-pyrophosphatase plays a more important role than H+-ATPase: the activity of the former increases 2.3-fold compared to the control osmotic conditions, whereas the activity of
H+-ATPase is practically unchanged. H+-pyrophosphatase was more responsive to the presence of exogenous NO donator and to variations in Ca2+ concentration. The effects of exogenous NO donator on tonoplast proton pumps depended on the concentration of Ca2+, which apparently can mediate NO action. 相似文献