全文获取类型
收费全文 | 55198篇 |
免费 | 4704篇 |
国内免费 | 1774篇 |
出版年
2023年 | 811篇 |
2022年 | 1177篇 |
2021年 | 1618篇 |
2020年 | 1940篇 |
2019年 | 2504篇 |
2018年 | 2210篇 |
2017年 | 1569篇 |
2016年 | 1576篇 |
2015年 | 1798篇 |
2014年 | 3366篇 |
2013年 | 3975篇 |
2012年 | 2536篇 |
2011年 | 3246篇 |
2010年 | 2409篇 |
2009年 | 2658篇 |
2008年 | 2870篇 |
2007年 | 2825篇 |
2006年 | 2373篇 |
2005年 | 2213篇 |
2004年 | 1996篇 |
2003年 | 1698篇 |
2002年 | 1457篇 |
2001年 | 994篇 |
2000年 | 820篇 |
1999年 | 881篇 |
1998年 | 804篇 |
1997年 | 663篇 |
1996年 | 638篇 |
1995年 | 631篇 |
1994年 | 608篇 |
1993年 | 497篇 |
1992年 | 465篇 |
1991年 | 403篇 |
1990年 | 319篇 |
1989年 | 300篇 |
1988年 | 249篇 |
1987年 | 262篇 |
1986年 | 202篇 |
1985年 | 365篇 |
1984年 | 489篇 |
1983年 | 420篇 |
1982年 | 444篇 |
1981年 | 361篇 |
1980年 | 369篇 |
1979年 | 295篇 |
1978年 | 227篇 |
1977年 | 223篇 |
1976年 | 220篇 |
1975年 | 190篇 |
1974年 | 166篇 |
排序方式: 共有10000条查询结果,搜索用时 347 毫秒
981.
Vytas K. Švedas Alexei L. Margolin Ilya V. Berezin 《Enzyme and microbial technology》1980,2(2):138-144
The equilibrium constants and the respective standard Gibbs energy changes for hydrolysis of some β-lactam antibiotics have been determined. Native and immobilized penicillin amidase (EC 3.5.1.11) from Escherichia coli has been used as a catalyst. The values of standard Gibbs energy changes corresponding to the pH-independent product of equilibrium concentrations (ΔG0c = ? RT ln Kc) have been calculated. The differences in the structure of the antibiotics nucleus hardly ever affect the value of the pH-independent component of the standard Gibbs energy change (ΔG0c) and value of apparent standard Gibbs energy change at a fixed pH (ΔG0′c). At the same time, the value of ΔG0c is more sensitive to the structure of the acyl moiety of the antibiotic; when ampicillin is used instead of benzylpenicillin, ΔG0c increases by ~6.3 kJ mol?1 (1.5 kcal mol?1). pH-dependences of the apparent standard Gibbs energy changes for hydrolysis of β-lactam antibiotics have been calculated. The pH-dependences of ΔG0′c for hydrolysis of all β-lactam antibiotics have a similar pattern. The thermodynamic pH optimum of the synthesis of these compounds is in the acid pH range (pH < 5.0). The breakage of the β-lactam ring leads to a sharp decrease in the ΔG0′c value and a change in the pattern of the pH-dependence. For example, at pH 5.0 ΔG0′c decreases from 14.4 kJ mol?1 for benzylpenicillin to ?1.45 kJ mol?1 for benzylpenicilloic acid. The reason for these changes is mainly a considerable increase in the pK of the amino group of the nucleus of the antibiotic and, as a consequence, a decrease in the component of standard Gibbs energy change, corresponding to the ionization of the system. The thermodynamic potentials of the enzymatic synthesis of semisynthetic penicillins and cephalosporins on the basis of both free acids and their derivatives (N-acylated amino acids, esters) are discussed. It is shown that with esters of the acids, a high yield of the antibiotic can, in principle, be achieved at higher pH values. 相似文献
982.
Graham S. Baldwin Alphonse Galdes H.Allen O. Hill Stephen G. Waley Edward P. Abraham 《Journal of inorganic biochemistry》1980,13(3):189-204
β-Lactamase II has two metal-binding sites. The electronic spectra of Cd(II)- and Co(II)-substituted β-lactamase II have been investigated. It is suggested that a thiol ligand is involved in metal binding at the first site. The stoichiometric dissociation constants for Co(II) binding to β-lactamase II were estimated to be 0.13 and 2.66 mM (pH 6.0, 4°C, 1 M NaCl) by equilibrium dialysis. Competition between Zn(II) and Co(II) for the first metal binding site suggests a value of 0.7 μM (pH 6.0, 30°C, 1 M NaCl) for the dissociation constant o Zn(II).The electronic spectra of the Co(II) enzyme lead to the suggestion that the coordination geometries around the metal ions in the first and second sites are related to those of a distorted tetrahedron and octahedron, respectively. 相似文献
983.
Ashwini Kumar M. M. Husain Hasan Mukhtar C. R. Krishna Murti 《Journal of biosciences》1980,2(3):181-189
Glutathione-S-transferase (EC 2.5.1.18) activity was assayed in hepatic and extra-hepatic tissues of pigeons using l-chloro-2,4-dinitrobenzene
and 1,2-dichloro-4-nitrobenzene as substrates. Gluthathione-S-transferase activity towards 1-chloro-2,4-dinitrobenzene in
pigeon was in the order: kidney > liver > testes > brain > lung> heart. The enzyme activity with 1-chloro-2,4-dinitrobenzene
as substrate was 40–44 times higher in pigeon liver and kidney than that observed with 1,2-dichloro-4-dinitrobenzene as substrate.K
m values of hepatic and renal glutathione transferase with l-chloro-2,4-dinitrobenzene as substrate were 2.5 and 3 mM respectively.
Double reciprocal plots with varying reduced gluthathione concentrations resulted in biphasic curves with twoK
m values (liver 0.31 mM and 4mM; kidney 0.36 mM and 1.3 mM). The enzyme activity was inhibited by oxidized gluthathione in
a dose-dependent pattern. 3-Methylcholanthrene elicited about 50% induction of hepatic glutathione transferase activity whereas
phénobarbital was ineffective. 相似文献
984.
Isolated hepatocytes from adult rats were cultured for 3 days in a serum-free synthetic medium. Supplementation with fibrinogen digests, glucagon and insulin remarkably increased DNA synthesis in hepatocytes. DNA synthesis began to increase at 35 h and reached a maximum at 41 to 54 h after plating. At this time, cells were morphologically identifiable as hepatocytes. Glucagon could be replaced by dibutyryl cyclic AMP or isobutyl-methyl-xanthine. Addition of amiloride (a Na+ influx inhibitor) during the initial 22 h completely inhibited DNA synthesis. These results suggest that influx of Na+ during early prereplicative period and increase in cellular cyclic AMP levels during late prereplicative period are necessary for the induction of DNA synthesis in hepatocytes. 相似文献
985.
986.
The 2′,3′-dialdehyde of ADP, obtained by periodate oxidation of ADP, inhibited the hydrolytic activity of the purified Ca2+, Mg2+-activated ATPase of . In the initial stages of the reaction inhibition was due to the reaction of 1 mol inhibitor/active site. When non-specific labelling of amino groups by the dialdehyde was lowered by the simultaneous presence of 15 mM ATP in the reaction mixture, 3 mol “ATP-protectable” binding sites/mol ATPase were found. “ATP-protectable” binding of the dialdehyde was not observed when the hydrolytically inactive ATPase of an mutant of was used although binding of the inhibitor to non-protected amino groups still occurred. This suggests that the mutant ATPase is unable to bind ATP or that the amino groups with which the dialdehyde reacts in the native enzyme are absent or masked. 相似文献
987.
3-(2-Carboxyethyl)thymine (3-CET) was synthesized from β-propiolactone (BPL) and dThd5′P at pH 9.0–9.5 via the intermediate 3-(2-carboxyethyl)thymidine-5′-monophosphoric acid (3-CEdThd5′P). 3-CEdThd5′P was converted to 3-CET by hydrolysis in 1.5 N HCl at 100°C for 2 h. The structure of 3-CET was assigned on the basis of UV spectra, electron impact (EI) and isobutane chemical ionization mass spectra and the EI mass spectrum of a trimethylsilyl derivative of 3-CET. BPL was reacted in vitro with calf thymus DNA at pH 7.5. 100 A units of BPL-reacted DNA yielded, following perchloric acid hydrolysis and preparative paper chromatography, 3 A units of 3-CET. Reaction of BPL with the phosphodiester thymidylyl-(3′-5′)thymidine gave 3-(2-carboxyethyl)thymidylyl-(3′-5′)-3-(2-carboxyethyl)thymidine (~3%). Phosphotriester formation was not detected. 相似文献
988.
Preparation and spectroscopic characterization of molecular species of brain phosphatidylserines 总被引:2,自引:0,他引:2
This study describes the first preparation and spectroscopic characterization of naturally occurring phospholipids separated according to degree of unsaturation. Phosphatidylserines (PS) have been prepared from bovine brain and shown to be pure by extensive thin layer chromatographic analysis as well as by infrared spectroscopy and fatty acid analysis. The PS has been separated according to degree of unsaturation and prepared using AgNO3-impregnated silica gel H thin-layer chromatography. Fatty acid analysis of the two principal PS subfractions indicates that they are enriched in the molecular species 1-octadecanoyl-2-docosahexaenoyl-sn-glycero-3-phosphorylserine and 1-octadecanoyl-2-octadecenoyl-sn-glycero-3-phosphorylserine. The identity of the two PS subfractions was further verified by rechromatographing on several thin layer systems and by infrared spectroscopy. With the use of a 100 MHz Fourier transform nuclear magnetic resonance (NMR) spectrometer, the spectra of bovine whole brain, white matter, gray matter, monoenoic, and hexaenoic PS were obtained. Distinct proton resonances were assigned to double bond protons, protons adjacent to a double bond, and protons between two double bonds, using fatty acid methyl ester standards. The various PS preparations gave different intensities of the various proton resonances which correlated with differences in fatty acid composition. The method provides a convenient, non-destructive spectroscopic method for distinguishing monoenoic and polyunsaturated species of intact phospholipids. Electron spin resonance studies of nitroxide-labelled cholestane in sonicated PS vesicles showed greater probe motion as the unsaturation of the acyl chains was increased. The hexaenoic PS vesicles were more fluid than monoenoic PS vesicles at all temperatures in the range 10-55 degrees C. These results suggest that neuronal membranes are more fluid than myelin membranes as neuronal membranes contain more hexaenoic phospholipids. 相似文献
989.
Andrzej J. Żelazowski Jadwiga A. Szymańska Czesklaw S. Cierniewski 《Chemico-biological interactions》1980,33(1):115-125
Two homogenous fractions of hepatic metallothioneins ((Cd,Zn) MT-1 and (Cd,Zn) MT-2) and renal metal binding proteins ((Bi,Cu) BP-1 and (Bi,Cu) BP-2) were isolated from rats exposed to heavy metals and specific antisera to them were produced in rabbits.These antisera were tested by immunodiffusion and immunoelectrophoresis for their ability to bind different fractions of hepatic Cd,Zn -metallothionein and renal (Bi,Cu)-, (Hg,Cu)- and (Cd,Cu)-binding proteins. It was found that anti (Bi,Cu) BP antisera did not cross-react with hepatic (Cd,Zn) MT-1 and (Cd,Zn) MT-2. Strong immunological cross-reactions were detected between anti (Bi,Cu) BP antisera and individual forms of (Cd,Cu)-, (Hg,Cu)- and (Bi,Cu)-binding proteins isolated from rat kidneys. 相似文献
990.
The phagocytosis of Trypanosoma cruzi bloodstream forms is mediated by macrophage Pronase-sensitive membrane components. Trypsin and chymotrypsin treatment of macrophages, which prevents the uptake of T. cruzi culture forms, does not inhibit the phagocytosis of bloodstream parasites. The phagocytosis activity of the macrophages was recovered within 6–8 hr after the removal of Pronase. Inhibition of protein synthesis after Pronase treatment prevents the recovery of the endocytic activity of the macrophages. Fc and C3b receptors are not apparently essential for the phagocytosis of T. cruzi bloodstream forms. The described membrane components may help to explain the tropism of some T. cruzi strains for cells of the mononuclear phagocytic system in the living host. 相似文献