全文获取类型
收费全文 | 6069篇 |
免费 | 658篇 |
国内免费 | 1篇 |
出版年
2022年 | 37篇 |
2021年 | 89篇 |
2020年 | 55篇 |
2019年 | 61篇 |
2018年 | 76篇 |
2017年 | 89篇 |
2016年 | 136篇 |
2015年 | 218篇 |
2014年 | 225篇 |
2013年 | 347篇 |
2012年 | 330篇 |
2011年 | 371篇 |
2010年 | 235篇 |
2009年 | 201篇 |
2008年 | 291篇 |
2007年 | 279篇 |
2006年 | 246篇 |
2005年 | 241篇 |
2004年 | 251篇 |
2003年 | 217篇 |
2002年 | 223篇 |
2001年 | 140篇 |
2000年 | 128篇 |
1999年 | 134篇 |
1998年 | 70篇 |
1997年 | 64篇 |
1996年 | 77篇 |
1995年 | 66篇 |
1994年 | 64篇 |
1993年 | 68篇 |
1992年 | 88篇 |
1991年 | 77篇 |
1990年 | 95篇 |
1989年 | 108篇 |
1988年 | 71篇 |
1987年 | 51篇 |
1986年 | 59篇 |
1985年 | 64篇 |
1984年 | 60篇 |
1983年 | 50篇 |
1982年 | 54篇 |
1981年 | 46篇 |
1980年 | 48篇 |
1979年 | 58篇 |
1978年 | 38篇 |
1977年 | 41篇 |
1976年 | 51篇 |
1975年 | 39篇 |
1974年 | 57篇 |
1973年 | 50篇 |
排序方式: 共有6728条查询结果,搜索用时 31 毫秒
51.
R D Beauchamp H M Sheng T Alam C M Townsend J Papaconstantinou 《Molecular endocrinology (Baltimore, Md.)》1992,6(11):1789-1796
52.
Administration of diisopropylfluorophosphate (DFP), an organophosphorus (OP) compound, irreversibly inhibits acetylcholinesterase (AChE) and results in cholinergic hyperactivity. This study investigated muscarinic and gamma-aminobutyric acid (GABA) receptor changes in visual cortex of cats following an acute exposure to DFP. A single acute administration of DFP (4 mg/kg) decreased the number of muscarinic receptors at 2, 10, and 20 hours after treatment. GABA receptors were elevated at 2 and 10 hours but returned to within control levels at 20 hours. No significant alteration in muscarinic or GABA receptor affinity was noted. In all cases cortical AChE activity was inhibited 60-90%. These findings show a down regulation of muscarinic receptors after DFP associated with low AChE activity. GABA receptors also are altered, and may be part of a compensatory mechanism to counteract excess cholinergic stimulation. 相似文献
53.
Thomas F. Holzman Christine C. Chung Rohinton Edalji David A. Egan Margaret Martin Earl J. Gubbins Grant A. Krafft Gary T. Wang A. Mitchel Thomas Saul H. Rosenberg et al. 《Journal of Protein Chemistry》1991,10(5):553-563
The kinetic behavior andpH-stability of recombinant human renin was analyzed using a new fluorogenic substrate based on the normal P6-P3 renin cleavage sequence in human angiotensinogen. The design of this fluorogenic substrate makes possible, for the first time, direct monitoring of the kinetics of proteolytic conversion of prorenin to renin. ThepH-stability profile for renin, measured with the substrate at 25°C, indicated a broad plateau of stability betweenpH 6.0 and 10.0. Analysis of thepH-activity profile of renin for the substrate indicated a minimumK
m
(1.8 µM) atpH 7.4 and a maximumV
m
betweenpH 7.4 and 8.0. The thermodynamics of the binding of a novel, soluble, peptidomimetic inhibitor to renin indicated it is possible to retain the tight-binding characteristics and enthalpy contributions to binding of larger peptide-derived inhibitors, while reducing inhibitor size and entropic contributions to binding. A novel derivative of the fluorogenic substrate, containing a 3-methyl histidine substitution at the P2 site, was used to test the recent hypothesis that renin functions by virtue of substrate-directed catalysis. 相似文献
54.
Antibiotic production by the marine photosynthetic bacterium Chromatium purpuratum NKPB 031704: localization of activity to the chromatophores 总被引:2,自引:0,他引:2
J.Grant Burgess Hideaki Miyashita Hiroaki Sudo Tadashi Matsunaga 《FEMS microbiology letters》1991,84(3):301-306
Abstract Over 200 strains of marine purple photosynthetic bacteria were isolated. Two strains showed antibiotic activity towards Saccharomyces cerevisiae and were tentatively identified as Chromatium purpuratum . Crude antibiotic, prepared by solvent extraction, showed a broad antimicrobial spectrum. The highest activity was found in the chromatophore fraction. Chromatographic separation of purified light harvesting complex from one strain, NKPB 031704, showed the presence of two separate pigmented compounds which were responsible for antimicrobial activity. Our findings reveal the unexpected ability of photosynthetic bacteria to produce broad spectrum antibiotics. In addition, this is the first example of intracellular localization of antibiotic activity in a marine bacterium. 相似文献
55.
Candida albicans and three other Candida species contain an elongation factor structurally and functionally analogous to elongation factor 3. 总被引:3,自引:0,他引:3
A cell-free poly(U)-dependent translation elongation system from Candida albicans is ATP-dependent due to the presence of an elongation factor 3 (EF3)-like activity. Saccharomyces cerevisiae ribosomes added to a C. albicans postribosomal supernatant (PRS) supported poly(U)-dependent elongation, suggesting that the C. albicans lysate contained a soluble translation factor functionally analogous to the S. cerevisiae translation factor EF-3. The presence of EF-3 in C. albicans was confirmed by Western blotting using an antibody raised against S. cerevisiae EF-3. This antibody was also used to screen a selection of Candida species, all of which possessed EF-3 with molecular mass in the range of 110-130 kDa. 相似文献
56.
P M Jordan M J Warren H J Williams N J Stolowich C A Roessner S K Grant A I Scott 《FEBS letters》1988,235(1-2):189-193
The dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase was specifically labelled with 13C by growth of the bacteria in the presence of 5-amino[5-13C]levulinic acid. Using 13C-NMR spectroscopy, the structure of the cofactor was confirmed as a dipyrromethane made up of two linked pyrrole rings each derived from porphobilinogen. The chemical shift data indicate that one of the pyrrole rings of the cofactor is covalently linked to the deaminase enzyme through a cysteine residue. Evidence from protein chemistry studies suggest that cysteine-242 is the covalent binding site for the cofactor. 相似文献
57.
The rat hepatoma cell line MH1C1 has been characterized to show a stimulated secretion of C-reactive protein in response to both leukocyte supernatant and a purified human interleukin-1 preparation. The time-dependency and dose-response relationship of CRP secretion were comparable to and somewhat more sensitive than the effects of leukocyte supernatant and purified human interleukin-1 on the proliferative rate of murine thymocytes; the proliferative rate of the hepatoma cell line MH1C1 was unchanged under these conditions. Agents which affect the thymocyte bioassay response to interleukin-1 namely interleukin-2, lipopolysaccharide, concanavalin A and phytohemagglutinin showed no effect on the C-reactive protein release of the MH1C1 cell line. These data strongly support the suitability of this cell line for the in vitro study of the hepatic acute phase stimulus-secretion response. 相似文献
58.
A J Grant I A Ramshaw P Badenoch-Jones R D Eichner N H Hunt 《European journal of biochemistry》1986,154(3):635-641
An inhibitor of plasminogen activator (PA) secreted by a tumorigenic, but non-metastatic, rat mammary adenocarcinoma cell line has been purified to apparent homogeneity and characterized. It strongly inhibited human urokinase, but was 100 times less potent in inhibiting bovine trypsin and had no effect on plasmin or thrombin. A secreted, urokinase-type PA (Mr 48 000) and a cell-associated PA from a metastatic rat adenocarcinoma cell line were also strongly inhibited. In contrast, a tissue-type PA (Mr 66 000), secreted by human melanoma cells, was only slightly inhibited. Purified inhibitor showed a band of Mr 66 000 in sodium dodecyl sulphate/polyacrylamide gel electrophoresis and an isoelectric point of 4.5 after chromatofocusing. The inhibition of human urokinase was non-competitive. 相似文献
59.
Thrombospondin (TSP) is a glycoprotein secreted from the alpha-granules of platelets upon activation. In the presence of divalent cations, the secreted protein binds to the surface of the activated platelets and is responsible for the endogenous lectin-like activity associated with activated platelets. Platelets fixed with formaldehyde following activation by thrombin are agglutinated by exogenously added TSP. Fixed, nonactivated platelets are not agglutinated. The platelet agglutinating activity of TSP is optimally expressed in the presence of 2 mM each of Mg2+ and Ca2+. Reduction of the disulfide bonds within the TSP molecule inhibits its platelet agglutinating activity. TSP bound to the surface of fixed, activated platelets can be eluted by the addition of disodium ethylenediaminetetraacetate. This approach was exploited to identify the region of the TSP molecule containing the platelet binding site. The binding site resides within a thermolytic fragment of TSP with Mr 140 000 but is not present in the Mr 120 000 fragment derived from the polypeptide of Mr 140 000. Since both the Mr 140 000 and 120 000 fragments contain fibrinogen binding sites, this finding suggests that the binding of TSP to the platelet surface requires interaction with other platelet surface components in addition to fibrinogen. The observation that fibrinogen only partially inhibits the TSP-mediated agglutination of fixed, activated platelets is consistent with this interpretation. 相似文献
60.
Different modes of ligand binding to the hepatic galactose/N-acetylgalactosamine lectin on the surface of rabbit hepatocytes 总被引:6,自引:0,他引:6
A study of the binding of three different 125I-labeled, galactose-terminated ligands to the hepatic galactose/N-acetylgalactosamine-specific lectin found on the surface of rabbit hepatocytes revealed that the different ligands manifest different physical parameters of binding. Asialoorosomucoid (125I-ASOR) binding was best described as involving two independent classes of binding sites on rabbit hepatocytes, with 161 000 sites/cell with a dissociation constant of 0.44 nM and 292 000 sites/cell with a Kd of 9.7 nM. Asialotriantennary glycopeptide purified from human alpha-1 protease inhibitor and modified with tyrosine at the N-terminus to permit radioiodination (TRI) [Lee, Y. C., Townsend, R. R., Hardy, M. R., L?nngren, J., Arnarp, J., Haraldsson, M., & L?nn, H. (1983) J. Biol. Chem. 258, 199-202] was also found to bind to two apparent classes of binding sites but with different binding parameters: 292 000 sites/cell of Kd = 1.47 nM and 982 000 sites/cell of Kd = 25.3 nM. A synthetic ligand, alpha,beta-diaspartamide of tris[(beta-lactosyloxy)methyl](6-aminohexanamido)methane (di-tris-lac) containing six nonreducing galactose residues [Lee, R. T., Lin, P., & Lee, Y. C. (1984) Biochemistry 23, 4255-4261], was found to bind to 817 000 sites/cell of Kd = 0.63 nM and 1.23 X 10(6) sites/cell of Kd = 25.3 nM. Thus, there were many more total binding sites for TRI or di-tris-lac on the surface of rabbit hepatocytes than there were for asialoorosomucoid, although the dissociation constants were similar for all three ligands.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献