全文获取类型
收费全文 | 7328篇 |
免费 | 907篇 |
国内免费 | 4篇 |
专业分类
8239篇 |
出版年
2021年 | 81篇 |
2018年 | 90篇 |
2017年 | 75篇 |
2016年 | 112篇 |
2015年 | 153篇 |
2014年 | 215篇 |
2013年 | 286篇 |
2012年 | 311篇 |
2011年 | 296篇 |
2010年 | 197篇 |
2009年 | 174篇 |
2008年 | 260篇 |
2007年 | 233篇 |
2006年 | 237篇 |
2005年 | 204篇 |
2004年 | 214篇 |
2003年 | 227篇 |
2002年 | 202篇 |
2001年 | 224篇 |
2000年 | 220篇 |
1999年 | 195篇 |
1998年 | 97篇 |
1997年 | 92篇 |
1995年 | 90篇 |
1994年 | 91篇 |
1993年 | 75篇 |
1992年 | 174篇 |
1991年 | 170篇 |
1990年 | 160篇 |
1989年 | 154篇 |
1988年 | 163篇 |
1987年 | 140篇 |
1986年 | 124篇 |
1985年 | 161篇 |
1984年 | 120篇 |
1983年 | 115篇 |
1982年 | 108篇 |
1981年 | 87篇 |
1980年 | 91篇 |
1979年 | 138篇 |
1978年 | 92篇 |
1977年 | 92篇 |
1976年 | 97篇 |
1975年 | 89篇 |
1974年 | 105篇 |
1973年 | 95篇 |
1972年 | 85篇 |
1971年 | 77篇 |
1969年 | 71篇 |
1968年 | 64篇 |
排序方式: 共有8239条查询结果,搜索用时 15 毫秒
61.
62.
63.
Botulinum neurotoxin type B. Its purification, radioiodination and interaction with rat-brain synaptosomal membranes 总被引:12,自引:0,他引:12
D M Evans R S Williams C C Shone P Hambleton J Melling J O Dolly 《European journal of biochemistry》1986,154(2):409-416
Neurotoxin from Clostridium botulinum type B was purified to homogeneity by by affinity and ion-exchange chromatography; specific neurotoxicity of this protein (Mr of approximately equal to 155 000) following trypsinisation attained a level of 2 X 10(8) mouse LD50 units/mg protein. 125I-iodination of the toxin to high specific radioactivities (19-63 TBq/mmol) yielded typically greater than 65% of its original toxicity; dodecyl sulphate gel electrophoresis under reducing conditions, after trypsinisation, showed that the larger polypeptide (Mr of approximately equal to 101 000) was labelled preferentially. Saturable binding of the 125I-labelled neurotoxin to rat cerebrocortical synaptosomes was observed and Scatchard analysis showed a low content of acceptors with high affinity (Kd = 0.3-0.5 nM;Bmax approximately equal to 30-60 fmol/mg protein, together with a much larger population of weak-affinity sites. No significant differences in binding affinity were seen in competition experiments using native or fully activated (trypsinized) neurotoxin, indicating that chain cleavage is not essential for acceptor-toxin interaction. Type A botulinum neurotoxin showed a limited capacity to inhibit the synaptosomal binding of labelled type B toxin, even at high concentrations (1 muM), and other neurotoxins were without effect, emphasising the acceptor selectivity. Near-complete loss of specific toxin binding was produced by preincubation of synaptosomes with neuraminidase whereas inhibition of the low-affinity sites with wheat-germ agglutinin was less pronounced; such inactivation was prevented by inclusion of selective inhibitors (2,3-dehydro-2-deoxy-N-acetylneuraminic acid and N-acetylglucosamine, respectively). These observations implicate N-acetylneuraminic acid and, possibly, other sugar moieties as constituents of the toxin acceptors. Trypsinisation of synaptosomes gave incomplete inhibition of binding when assayed with 1 nM or 10 nM 125I-iodinated toxin. Detailed analysis of the actions of neuraminidase, trypsin and heat treatment on the concentration dependence of toxin binding suggest the existence of at least two distinguishable populations of sites that contain N-acetylneuraminic acid, with a protein component being associated with the acceptors of lower affinity. These findings are discussed in relation to those previously reported for type A neurotoxin and to the possible physiological significance of such membrane acceptors. 相似文献
64.
J N Evans R C Davies A S Boyd I Ichinose N E Mackenzie A I Scott R L Baxter 《Biochemistry》1986,25(4):896-904
High-field NMR spectroscopic methods have been applied to study the reactions catalyzed by porphobilinogen (PBG) deaminase and uroporphyrinogen III (uro'gen III) cosynthase, which are the enzymes responsible for the formation of the porphyrin macrocycle. The action of these enzymes in the conversion of PBG, [2,11-13C]PBG, and [3,5-13C]PBG to uro'gens I and III has been followed by 1H and 13C NMR, and assignments are presented. The principal intermediate that accumulated was the correspondingly labeled (hydroxymethyl)bilane (HMB), the assignments for which are also presented. 相似文献
65.
J V Bartolome M B Bartolome L A Daltner C J Evans J D Barchas C M Kuhn S M Schanberg 《Life sciences》1986,38(25):2355-2362
Ornithine decarboxlyase (ODC) catalyzes the initial step in the bio-synthesis of the polyamines spermidine and spermine, which are key regulators of cell growth, proliferation and differentiation. Intracisternal administration of beta-endorphin (1 microgram) to 6 day-old rats markedly decreased brain, liver, heart and kidney ODC activity. Conversely, subcutaneous administration of beta-endorphin increased ODC activity in the heart and liver. Thus, ODC inhibition in peripheral organs in rat pups given beta-endorphin intracisternally appears to reflect central effects of this neuropeptide. Experiments were also carried out to test whether opioid receptors are involved in these tissue ODC responses. Naloxone prevented the decreases in brain ODC indicating the participation of opioid receptors in that process. In contrast, naloxone did not alter ODC responses in peripheral organs in rat pups given beta-endorphin intracisternally, indicating that these effects are independent of its classical opioid character. These results support the view that endogenous beta-endorphin may play an important role in organogenesis by modulating the growth-related enzyme ODC. The data also suggest that the regulation of peripheral organ development by beta-endorphin may be mediated through the release of growth regulatory substances from the CNS. 相似文献
66.
Purified lipoteichoic acids (LTAs) from several gram-positive organisms have been shown, by methods involving spectral changes of an added merocyanine dye probe, to have critical micelle concentrations in the range of 1 to 10 micrograms/ml, suggesting that acylated LTAs in their monomer forms may represent the major configuration of extracellular LTAs in bacterial culture fluids. The critical micelle concentrations obtained did not differ markedly with degree of carbohydrate substitution of the polymers. The significance of these findings in relation to the biological properties of LTA is discussed. 相似文献
67.
13C NMR spectroscopy of Methanobacterium thermoautotrophicum. Carbon fluxes and primary metabolic pathways 总被引:2,自引:0,他引:2
J N Evans D P Raleigh C J Tolman M F Roberts 《The Journal of biological chemistry》1986,261(35):16323-16331
The flux of 13C-labeled carbons from the soluble metabolite 2,3-cyclopyrophosphoglycerate (CPP), a novel compound found in high concentrations exclusively in methanobacteria and methanobrevibacter, into carbohydrate-containing material has been deduced by solid-state 13C NMR spectroscopy which strongly argues for a role in gluconeogenesis for this unique metabolite. The turnover rates, but not the steady-state levels, of CPP labeled by 13CO2 or [13C]acetate depend dramatically on cell growth conditions. When the demand for carbohydrate synthesis is reduced (i.e. in stationary phase), the rates of CPP biosynthesis and degradation decrease 10-fold, and the disaccharide alpha, alpha-trehalose accumulates. Valinomycin, a metabolic inhibitor of Methanobacterium thermoautotrophicum growth, does not affect steady-state levels of CPP, but does decrease 13C uptake into the CPP pool. The effects of these different conditions on CPP labeling suggest stringent regulation of CPP linked to cellular metabolism. Labeling of CPP by [6-(13)C]glucose, which does not serve as an energy or carbon source for this organism, provides strong evidence that glucose is cleaved by the reverse of the gluconeogenesis pathway. This metabolic pathway linking glucose with triose phosphate type precursors and an analysis of the 13C NMR spectrum of CPP labeled by incubating cells with [U-13C]glucose have established that in vivo phosphoenolpyruvate synthetase must be reversible. 相似文献
68.
Evans W. J.; Meredith C. N.; Cannon J. G.; Dinarello C. A.; Frontera W. R.; Hughes V. A.; Jones B. H.; Knuttgen H. G. 《Journal of applied physiology》1986,61(5):1864-1868
The effects of one 45-min bout of high-intensity eccentric exercise (250 W) were studied in four male runners and five untrained men. Plasma creatine kinase (CK) activity in these runners was higher (P less than 0.001) than in the untrained men before exercise and peaked at 207 IU/ml 1 day after exercise, whereas in untrained men the maximum was 2,143 IU/ml 5 days after exercise. Plasma interleukin-1 (IL-1) in the trained men was also higher (P less than 0.001) than in the untrained men before exercise but did not significantly increase after exercise. In the untrained men, IL-1 was significantly elevated 3 h after exercise (P less than 0.001). In the untrained group only, 24-h urines were collected before and after exercise while the men consumed a meat-free diet. Urinary 3-methylhistidine/creatinine in the untrained group rose significantly from 127 mumol/g before exercise to 180 mumol/g 10 days after exercise. The results suggest that in untrained men eccentric exercise leads to a metabolic response indicative of delayed muscle damage. Regularly performed long distance running was associated with chronically elevated plasma IL-1 levels and serum CK activities without acute increases after an eccentric exercise bout. 相似文献
69.
C R Mendelson E E Wright C T Evans J C Porter E R Simpson 《Archives of biochemistry and biophysics》1985,243(2):480-491
Aromatase cytochrome P-450 (P-450AROM) was partially purified from human placental microsomes by hydrophobic affinity chromatography using Phenyl-Sepharose and ion-exchange chromatography on DEAE-cellulose. The resulting preparation had a specific activity of 2 nmol/mg protein with respect to cytochrome P-450 content and displayed a type I difference spectrum upon addition of the substrate androstenedione. When the cytochrome P-450-enriched fractions were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and stained with Coomassie blue, there was an enrichment of two proteins having apparent molecular weights of 50,000 and 55,000. The bands containing these proteins were removed from unstained polyacrylamide gels and injected separately or together into three rabbits. An aliquot of the serum or an immunoglobulin (IgG) fraction prepared from the serum of the rabbit injected with the 55-kDa band or with both the 50- and 55-kDa bands inhibited aromatase activity of human placental microsomes by 80%; this IgG had no effect on 17 alpha-hydroxylase or 21-hydroxylase activities of human fetal adrenal microsomes. In contrast, the serum of the rabbit injected with the 50-kDa band had little capacity to inhibit placental aromatase activity. By immunoblot analysis, it was found that the IgG from the serum of the rabbit immunized with the 55-kDa protein bound specifically to a protein of 55 kDa in human placental microsomes. Monoclonal antibodies were prepared from a hybridoma cell line derived from the spleen cells of mice immunized against the 55-kDa protein. The monoclonal IgG was covalently linked to a Sepharose 4B column and was used for immunoaffinity chromatography of cytochrome P-450AROM. The finding that cytochrome P-450 and the 55-kDa protein were selectively retained by the affinity column and eluted with NaCl (2 M) and glycine (0.2 M, pH 3.0) and that this fraction contained aromatase activity upon reconstitution with purified NADPH-cytochrome P-450 reductase and phospholipid, is indicative that the 55-kDa protein is indeed cytochrome P-450AROM. These findings are also indicative that both the monoclonal and polyclonal IgGs are specific for human cytochrome P-450AROM. 相似文献
70.
Defective in vitro T cell colony formation in the acquired immunodeficiency syndrome 总被引:7,自引:0,他引:7
A Winkelstein R S Klein T L Evans B W Dixon W L Holder L D Weaver 《Journal of immunology (Baltimore, Md. : 1950)》1985,134(1):151-156
Depressed T cell immunity is a universal characteristic of the acquired immunodeficiency syndrome (AIDS). In the present study, 25 patients with AIDS and opportunistic infections, 22 individuals with AIDS-related complex (ARC, or chronic lymphadenopathy syndrome), and 20 healthy homosexuals were evaluated by means of the T cell colony assay. Forty-seven healthy heterosexual controls showed an average of 3964 +/- 319 colonies/7.5 X 10(5) cells, with a range of 880 to 9340. The mean in the 20 healthy homosexuals (3173 +/- 483) did not differ significantly from the controls; in this group, only three patients had values less than 1000 colonies/plate. By contrast, all AIDS patients and 14 ARC patients had colony counts less than 1000. The mean value for the AIDS patients was only 24 +/- 15 (p less than 0.0005 compared with either controls or healthy homosexuals); values in the ARC group were intermediate (1180 +/- 360). The addition of interleukin 2 to the plates promoted correction of the proliferative abnormality in ARC patients. This interleukin increased colony scores in the AIDS group, but the mean value was still significantly less than controls. Comparison indicated that the colony assay is a more sensitive indicator for detecting proliferative abnormalities than responses to PHA, Con A, or pokeweed mitogen in suspension cultures. 相似文献