全文获取类型
收费全文 | 5033篇 |
免费 | 564篇 |
出版年
2022年 | 34篇 |
2021年 | 75篇 |
2020年 | 47篇 |
2019年 | 49篇 |
2018年 | 61篇 |
2017年 | 69篇 |
2016年 | 113篇 |
2015年 | 173篇 |
2014年 | 179篇 |
2013年 | 271篇 |
2012年 | 283篇 |
2011年 | 323篇 |
2010年 | 204篇 |
2009年 | 170篇 |
2008年 | 239篇 |
2007年 | 230篇 |
2006年 | 209篇 |
2005年 | 196篇 |
2004年 | 196篇 |
2003年 | 184篇 |
2002年 | 199篇 |
2001年 | 115篇 |
2000年 | 103篇 |
1999年 | 115篇 |
1998年 | 63篇 |
1997年 | 53篇 |
1996年 | 68篇 |
1995年 | 56篇 |
1994年 | 59篇 |
1993年 | 61篇 |
1992年 | 65篇 |
1991年 | 53篇 |
1990年 | 70篇 |
1989年 | 87篇 |
1988年 | 56篇 |
1987年 | 41篇 |
1986年 | 46篇 |
1985年 | 50篇 |
1984年 | 50篇 |
1983年 | 40篇 |
1982年 | 50篇 |
1981年 | 40篇 |
1980年 | 37篇 |
1979年 | 49篇 |
1978年 | 33篇 |
1977年 | 35篇 |
1976年 | 49篇 |
1975年 | 33篇 |
1974年 | 52篇 |
1973年 | 42篇 |
排序方式: 共有5597条查询结果,搜索用时 31 毫秒
41.
D. A. McCarthy I. Macdonald M. Grant M. Marbut M. Watling S. Nicholson J. J. Deeks A. J. Wade J. D. Perry 《European journal of applied physiology and occupational physiology》1992,64(6):513-517
Eight healthy male volunteers exercised for two 30-min sessions starting 3 h apart on an electronically braked cycle ergometer at a work load (mean 155.9 W, SD 33.4 W) which required an oxygen consumption that was 70% of their maximal rate of oxygen uptake. Venous blood samples were taken through an indwelling cannula over a period of 6 h beginning shortly before the first bout of exercise and were analysed for routine haematological parameters and for lactate, noradrenaline, adrenaline and cortisol. Both bouts of exercise induced an immediate leucocytosis due to rises in lymphocytes and neutrophils but only the first exercise bout induced a substantial delayed neutrophilia. In at least five subjects, changes in lymphocyte and platelet numbers were correlated (Spearman's rank procedure, P less than 0.05) with simultaneous changes in the plasma concentrations of lactate, noradrenaline and adrenaline over the 6-h period studied. Increases in the plasma concentration of cortisol due to exercise correlated positively with the percentage changes in neutrophil numbers at 3 h and 6 h. These results are consistent with the suggestion that the immediate and delayed leucocytosis induced by exercise are mediated respectively by catecholamine and by cortisol. 相似文献
42.
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
43.
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
44.
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
45.
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
46.
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
47.
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
48.
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
49.
Studies on the maintenance of cytochromes P-450 and b5, monooxygenases and cytochrome reductases in primary cultures of rat hepatocytes 总被引:2,自引:0,他引:2
The cytochrome P-450 content of rat hepatocytes declined rapidly over 72 h in culture, due primarily to denaturation to cytochrome P-420. Six different media were investigated for their ability to conserve cytochrome P-450 during culture, and the most successful was a modified Earle's medium. After 72 h culture in this medium, cytochromes P-450 and b5, NADH-cytochrome b5- and NADPH-cytochrome c-reductases were maintained at 40, 100, 35 and 52% of fresh cell values, respectively. Cytochrome P-450 showed differential functional stability during culture with ethoxyresorufin O-deethylation being more stable than either pentoxyphenoxazone O-depentylation or biphenyl 4-hydroxylation. Monooxygenase than did cytochrome P-450 content. This discrepancy was not explained by loss of flavin nucleotides, FMN or FAD. 相似文献
50.
Mapping of epitopes for monoclonal antibodies against human platelet thrombospondin with electron microscopy and high sensitivity amino acid sequencing 总被引:21,自引:13,他引:8 下载免费PDF全文
N J Galvin V M Dixit K M O'Rourke S A Santoro G A Grant W A Frazier 《The Journal of cell biology》1985,101(4):1434-1441
A panel of monoclonal antibodies (Mab's) has been raised against human platelet thrombospondin (TSP). One Mab, designated A2.5, inhibits the hemagglutinating activity of TSP and immunoprecipitates the NH2 terminal 25 kD heparin binding domain of TSP (Dixit, V.M., D. M. Haverstick, K. M. O'Rourke, S. W. Hennessy, G. A. Grant, S. A. Santoro, and W. A. Frazier, 1985, Biochemistry, in press). Another Mab, C6.7, blocks the thrombin-stimulated aggregation of live platelets and immunoprecipitates an 18-kD fragment distinct from the heparin binding domain (Dixit, V. M., D. M. Haverstick, K. M. O'Rourke, S. W. Hennessy, G. A. Grant, S. A. Santoro, and W. A. Frazier, 1985, Proc. Natl. Acad. Sci. 82: 3472-3476). To determine the relative locations of the epitopes for these Mabs in the three-dimensional structure of TSP, we have examined TSP-Mab complexes by electron microscopy of rotary-shadowed proteins. The TSP molecule is composed of three 180-kD subunits, each of which consists of a small globular domain (approximately 8 nm diam) and a larger globular domain (approximately 16 nm diam) connected by a thin, flexible strand. The subunit interaction site is on the thin connecting strands, nearer the small globular domains. Mab A2.5 binds to the cluster of three small domains, indicating that this region contains the heparin binding domain and thus represents the NH2 termini of the TSP peptide chains. Mab C6.7 binds to the large globular domains on the side opposite the point at which the connecting strand enters the domain, essentially the maximum possible distance from the A2.5 epitope. Using high sensitivity automated NH2 terminal sequencing of TSP chymotryptic peptides we have ordered these fragments within the TSP peptide chain and have confirmed that the epitope for C6.7 in fact lies near the extreme COOH terminus of the peptide chain. In combination with other data, we have been able to construct a map of the linear order of the identified domains of TSP that indicates that to a large extent, the domains are arranged co-linearly with the peptide chain. 相似文献