全文获取类型
收费全文 | 2002篇 |
免费 | 49篇 |
国内免费 | 40篇 |
出版年
2023年 | 5篇 |
2022年 | 13篇 |
2021年 | 27篇 |
2020年 | 19篇 |
2019年 | 41篇 |
2018年 | 35篇 |
2017年 | 17篇 |
2016年 | 29篇 |
2015年 | 87篇 |
2014年 | 183篇 |
2013年 | 161篇 |
2012年 | 166篇 |
2011年 | 181篇 |
2010年 | 112篇 |
2009年 | 94篇 |
2008年 | 67篇 |
2007年 | 87篇 |
2006年 | 75篇 |
2005年 | 69篇 |
2004年 | 48篇 |
2003年 | 68篇 |
2002年 | 39篇 |
2001年 | 21篇 |
2000年 | 25篇 |
1999年 | 18篇 |
1998年 | 27篇 |
1997年 | 24篇 |
1996年 | 20篇 |
1995年 | 28篇 |
1994年 | 35篇 |
1993年 | 18篇 |
1992年 | 23篇 |
1991年 | 17篇 |
1990年 | 22篇 |
1989年 | 17篇 |
1988年 | 13篇 |
1987年 | 8篇 |
1986年 | 9篇 |
1985年 | 18篇 |
1984年 | 21篇 |
1983年 | 19篇 |
1982年 | 16篇 |
1981年 | 12篇 |
1980年 | 16篇 |
1979年 | 10篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 7篇 |
1975年 | 4篇 |
1972年 | 3篇 |
排序方式: 共有2091条查询结果,搜索用时 31 毫秒
11.
In this study we compared the properties of cytochrome-c oxidase (COX) in cultured fibroblasts from two patients with Leigh Syndrome with COX from control fibroblasts. The fibroblasts from patients showed decreased growth reates and elevated lactate production. COX activity of patients fibroblasts was about 25% of control. Kinetic studies with isolated mitochondria showed a higher Km for cytochrome c and a markedly reduced molecular turnover of COX from patients, indicating a different structure of the enzyme. A biphasic change of COX activity was obtained by titration of dodecylmaltoside solubilized mitochondria from control fibroblasts with increasing concentrations of anions. With patient mitochondria we found only the inhibiting phase of COX activity and, in contrast to control mitochondria, irreversible inhibition of COX activity by guanidinium chloride. ELISA titrations with monoclonal antibodies to subunit II, IV, Vab, VIac and VIIab indicated a normal amount of mitochondrial coded subunit II, but a reduced amound of nuclear coded subunits. The data indicate incompletely assembled nuclear coded subunits of COX from patient fibroblasts. 相似文献
12.
Kwan-Fu Rex Sheu James C. K. Lai Young Tai Kim† Gary Dorante Jennifer Bagg 《Journal of neurochemistry》1985,44(2):593-599
Pyruvate dehydrogenase complex (PDHC) in rat brain was studied immunochemically, using antibodies against the bovine kidney PDHC, by immunoblotting, immunoprecipitation, inhibition of enzyme activity, and enzyme-linked immunoabsorbent assay (ELISA). The immunoblots showed that the antibodies bound strongly to the alpha peptide of the pyruvate dehydrogenase (E1) component, and to the dihydrolipoyl transacetylase (E2) and the dihydrolipoyl dehydrogenase (E3) components of PDHC. A similar immunoblotting pattern was observed in all eight brain regions examined. On immunoblotting of the subcellular fractions, these PDHC peptides were observed in mitochondria and synaptosomes but not in the postmitochondrial supernatants. This agrees with other evidence that brain PDHC is localized in the mitochondria. These results, together with those from sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoprecipitin, also showed that the alpha E1, beta E1, and E3 peptides of rat brain PDHC are very similar in sizes to those of the bovine kidney PDHC, being 42, 36, and 58 kD, respectively. The size of the E2 peptide, 66 kD, is different from that of bovine kidney E2, 73 kD. The relative abundance of PDHC protein in nonsynaptic mitochondria was compared by enzyme activity titration and ELISA. Both methods demonstrated that the amount of PDHC antigen in the mitochondria from cerebral cortex is greater than that in the olfactory bulb mitochondria. This is consistent with the results of the activity measurement. The ELISA also showed that the PDHCs in both mitochondrial populations are antigenically similar.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
13.
Samuel H. K. Ho Uttam Das Gupta John S. Rieske 《Journal of bioenergetics and biomembranes》1985,17(5):269-282
Deformamidoazidoantimycin A (DAA), a photoactive derivative of antimycin A containing an azido group substituting for the formamido group attached to the phenyl ring, was synthesized. The ultraviolet spectrum of DAA was almost identical to that of antimycin A, indicating little alteration of the electronic structure of the substituted phenyl ring by the azido substitution. However, the inhibitory effectiveness of DAA toward ubiquinol-cytochromec reductase (Complex III) purified from bovine heart (K
i
=ca. 0.5 µM) was considerably less than that of antimycin (K
i
3 pM), indicating a direct rather than a supporting role of the formamido group in the inhibitory activity of antimycin. Exposure of purified Complex III to [3H]DAA plus ultraviolet light caused a major labeling by tritium of SDS-PAGE band 7 (m=13 kDa by SDS-PAGE) and lesser but significant labeling of bands 3, 6, 8, and 9. Pretreatment of Complex III with antimycin greatly suppressed the labeling of bands 5, 6, and 7 but caused an apparent increased labeling of bands 8 and 9 by [3H]DAA, respectively. The labeling of band 7 by [3H]DAA also was strongly suppressed by reduction of Complex III by either sodium borohybride or ascorbate. Based on magnitude of labeling by [3H]DAA and the degree of suppression of labeling by antimycin, the protein of band 7 qualified as the principal component for specific binding of antimycin with the protein of band 6 (m=16 kDa) showing a lesser but significant amount of specific binding. 相似文献
14.
15.
A method is described to measure directly in rat brain the activity of pyruvate dehydrogenase kinase (PDHa kinase; EC 2.7.1.99), which catalyzes the inactivation of pyruvate dehydrogenase complex (PDHC, EC 1.2.4.1, EC 2.3.1.12, and EC 1.6.4.3). The activity showed the expected dependence on added ATP and divalent cation, and the expected inhibition by dichloroacetate, pyruvate, and thiamin pyrophosphate. These results, and the properties of pyruvate dehydrogenase phosphate phosphatase (EC 3.1.3.43), indicate that the mechanisms of control of phosphorylation of PDHC seem qualitatively similar in brain to those in other tissues. Regionally, PDHa kinase is more active in cerebral cortex and hippocampus, and less active in hypothalamus, pons and medulla, and olfactory bulbs. Indeed, the PDHa kinase activity in olfactory bulbs is uniquely low, and is more sensitive to inhibition by pyruvate and dichloroacetate than that in the cerebral cortex. Thus, there are significant quantitative differences in the enzymatic apparatus for controlling PDHC activity in different parts of the brain. 相似文献
16.
Effects of solubilisation on some properties of the membrane-bound respiratory enzyme D-amino acid dehydrogenase of Escherichia coli 总被引:3,自引:0,他引:3
Solubilisation, delipidation and partial purification of the membrane-bound enzyme D-amino acid dehydrogenase of Escherichia coli K12 produced significant changes in several of its properties. Solubilised enzyme showed a broader substrate specificity, increased affinity for at least three substrates, and a lower pH optimum with D-alanine as substrate. Solubilised enzyme was more heat-labile than native enzyme, particularly at 37 degrees C, and re-binding to envelope preparations restored protection against heat denaturation. Activity of delipidated enzyme could be increased by addition of pure phospholipids. Native enzyme showed biphasic Arrhenius kinetics associated with phase changes of membrane lipids. 相似文献
17.
Abstract: The activity of the pyruvate carboxylase was determined in brains of newborn and adult mice as well as primary cultures of astrocytes, of cerebral cortex neurons, and of cerebellar granule cells. The activity was found to be 0.25 ± 0.14, 1.24 ± 0.07, and 1.75 ± 0.13 nmol · min−1 · mg−1 protein in, respectively, neonatal brain, adult brain, and astrocytes. Neither of the two types of neurons showed any detectable enzyme activity (i.e., < 0.05 nmol · min−1 · mg−1 ). It is therefore concluded that pyruvate carboxylase is an astrocytic enzyme. 相似文献
18.
Effect of Dichloroacetate on Regional Energy Metabolites and Pyruvate Dehydrogenase Activity During Ischemia and Reperfusion in Gerbil Brain 总被引:1,自引:1,他引:0
The objective of this study was to determine whether administration of dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDH), improves recovery of energy metabolites following transient cerebral ischemia. Gerbils were pretreated with DCA, and cerebral ischemia was produced using bilateral carotid artery occlusion for 20 min, followed by reperfusion up to 4 h. DCA had no effect on the accumulation of lactic acid and the decrease in ATP and phosphocreatine (PCr) during the 20-min insult, nor on the recovery of these metabolites measured at 20 and 60 min reperfusion. However, at 4 h reperfusion, levels of ATP and PCr were significantly higher in DCA-treated animals than in controls, as PCr exhibited a secondary decrease in caudate nucleus of control animals. PDH was markedly inhibited at 20 min reperfusion in both groups, but was reactivated to a greater extent in DCA-treated animals at 60 min and 4 h reperfusion. These results demonstrate that DCA had no effect on the initial recovery of metabolites following transient ischemia. However, later in reperfusion, DCA enhanced the postischemic reactivation of PDH and prevented the secondary failure of energy metabolism in caudate nucleus. Thus, inhibition of PDH may limit the recovery of energy metabolism following cerebral ischemia. 相似文献
19.
A new bacterial alcohol dehydrogenase active on degraded lignin and several low molecular weight aromatic compounds 总被引:1,自引:0,他引:1
Jean Pelmont Catherine Tournesac Ahmed Mliki Michel Barrelle Claude Beguin 《FEMS microbiology letters》1989,57(1):109-114
A new intracellular bacterial dehydrogenase has been purified. It was active in the reversible reduction by NADH of conjugated carbonyl groups in partially degraded lignin. It was also active on various aromatic aldehydes such as vanillin, syringaldehyde and cinnamaldehyde, but had no effect on acetovanillone and lignin models carrying a conjugated ketone. It is proposed that this enzyme functions as a broadly specific lignin dehydrogenase at the level of aldehydic groups that are present in the lignin preparations. 相似文献
20.
Ascorbate-Stimulated Lipid Peroxidation in Human Brain Is Dependent on Iron but Not on Hydroxyl Radical 总被引:1,自引:0,他引:1
Abstract: The time dependence of N -acetyl-aspartate (NAA) concentrations relative to lactate and pyruvate in the injured rat spinal cord was investigated. Segments of spinal cord from regions rostral, caudal, and at the epicenter of the injury were analyzed. NAA concentrations were determined by gas chromatography-mass spectrometry and lactate and pyruvate concentrations were determined by UV spectroscopy at 20 min, 60 min, 2 h, 8 h, 24 h, 3 days, and 1 week after injury. NAA levels fell most significantly at the epicenter of the injury, reaching 30% of basal levels within 24 h. In all segments, lactate levels increased significantly shortly after injury, peaking at two to five times normal basal levels between 20 and 60 min after injury. Rostral and caudal to the injury site, lactate elevations and NAA reductions were less dramatic. Pyruvate concentrations were not significantly altered in any of the sections after injury. The temporal and spatial relationships of NAA and lactate changes indicated that ischemic conditions due to injury in the upper thoracic rat spinal cord were distributed asymmetrically. Acute ischemia was more severe caudal to the injury site, and NAA concentrations were more severely impaired in the rostral direction. The results suggest that the extent of neuronal degeneration due to spinal cord injury does not correlate directly with acute ischemic severity as measured by the lactate/pyruvate ratio, and may be more closely related to secondary changes in the neuronal environment. 相似文献