全文获取类型
收费全文 | 3431篇 |
免费 | 31篇 |
国内免费 | 63篇 |
专业分类
3525篇 |
出版年
2023年 | 16篇 |
2022年 | 16篇 |
2021年 | 19篇 |
2020年 | 39篇 |
2019年 | 63篇 |
2018年 | 91篇 |
2017年 | 26篇 |
2016年 | 29篇 |
2015年 | 91篇 |
2014年 | 194篇 |
2013年 | 185篇 |
2012年 | 149篇 |
2011年 | 219篇 |
2010年 | 196篇 |
2009年 | 198篇 |
2008年 | 213篇 |
2007年 | 232篇 |
2006年 | 130篇 |
2005年 | 117篇 |
2004年 | 145篇 |
2003年 | 106篇 |
2002年 | 86篇 |
2001年 | 35篇 |
2000年 | 53篇 |
1999年 | 43篇 |
1998年 | 40篇 |
1997年 | 40篇 |
1996年 | 37篇 |
1995年 | 38篇 |
1994年 | 42篇 |
1993年 | 42篇 |
1992年 | 32篇 |
1991年 | 27篇 |
1990年 | 22篇 |
1989年 | 14篇 |
1988年 | 19篇 |
1987年 | 30篇 |
1986年 | 13篇 |
1985年 | 27篇 |
1984年 | 45篇 |
1983年 | 54篇 |
1982年 | 71篇 |
1981年 | 45篇 |
1980年 | 44篇 |
1979年 | 38篇 |
1978年 | 27篇 |
1977年 | 22篇 |
1976年 | 21篇 |
1975年 | 9篇 |
1974年 | 16篇 |
排序方式: 共有3525条查询结果,搜索用时 0 毫秒
1.
Natalia Ermak Bernard Lacour Françoise Goirand Stéphanie Vicca 《Biochemical and biophysical research communications》2010,393(4):783-787
We compared the apoptotic mechanism involved in U937 human monocytic cell line in presence of oxidized low-density lipoproteins (oxLDL) obtained after treatment with hypochlorous acid (HOCl) or copper (Cu).Both types of oxLDL induced U937 apoptotic cell death via the mitochondrial pathway. In contrast to HOCl-oxLDL, Cu-oxLDL induced apoptosis via a caspase-independent mechanism, with no activation of pro-caspase-3, but via the release of apoptosis inducing factor (AIF) from mitochondria.The apoptotic program of the monocyte differs depending on the mode of LDL oxidation, based on differences in the oxidatively modified components of the two oxLDL types. 相似文献
2.
R.J. Ulvik I. Romslo F. Roland R.R. Crichton 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,677(1):50-56
Mitochondria mobilize iron from ferritin by a mechanism that depends on external FMN. With rat liver mitochondria, the rate of mobilization of iron is higher from rat liver ferritin than from horse spleen ferritin. With horse liver mitochondria, the rate of iron mobilization is higher from horse spleen ferritin than from rat liver ferritin. The results are explained by a higher affinity between mitochondria and ferritins of the same species. The mobilization of iron increases with the iron content of the ferritin and then levels off. A maximum is reached with ferritins containing about 1 200 iron atoms per molecule. The results represent further evidence that ferritin may function as a direct iron donor to the mitochondria. 相似文献
3.
Toxicity of Dopamine to Striatal Neurons In Vitro and Potentiation of Cell Death by a Mitochondrial Inhibitor 总被引:8,自引:2,他引:6
B. A. McLaughlin †D. Nelson †‡M. Ereciska † M.-F. Chesselet 《Journal of neurochemistry》1998,70(6):2406-2415
Abstract: Intrastriatal injections of the mitochondrial toxins malonate and 3-nitropropionic acid produce selective cell death similar to that seen in transient ischemia and Huntington's disease. The extent of cell death can be attenuated by pharmacological or surgical blockade of cortical glutamatergic input. It is not known, however, if dopamine contributes to toxicity caused by inhibition of mitochondrial function. Exposure of primary striatal cultures to dopamine resulted in dose-dependent death of neurons. Addition of medium supplement containing free radical scavengers and antioxidants decreased neuronal loss. At high concentrations of the amine, cell death was predominantly apoptotic. Methyl malonate was used to inhibit activity of the mitochondrial respiratory chain. Neither methyl malonate (50 µ M ) nor dopamine (2.5 µ M ) caused significant toxicity when added individually to cultures, whereas simultaneous addition of both compounds killed 60% of neurons. Addition of antioxidants and free radical scavengers to the incubation medium prevented this cell death. Dopamine (up to 250 µ M ) did not alter the ATP/ADP ratio after a 6-h incubation. Methyl malonate, at 500 µ M , reduced the ATP/ADP ratio by ∼30% after 6 h; this decrease was not augmented by coincubation with 25 µ M dopamine. Our results suggest that dopamine causes primarily apoptotic death of striatal neurons in culture without damaging cells by an early adverse action on oxidative phosphorylation. However, when combined with minimal inhibition of mitochondrial function, dopamine neurotoxicity is markedly enhanced. 相似文献
4.
Little is known about the biological functions of the phospholipase A2 receptor (PLA2R1) except that it has the ability to bind a few secreted phospholipases A2 (sPLA2′s). We have previously shown that PLA2R1 regulates senescence in normal human cells. In this study, we investigated the ability of PLA2R1 to control cancer cell growth. Analysis of expression in cancer cells indicates a marked PLA2R1 decrease in breast cancer cell lines compared to normal or nontransformed human mammary epithelial cells. Accordingly, PLA2R1 ectopic expression in PLA2R1-negative breast cancer cell lines led to apoptosis, whereas a prosenescence response was predominantly triggered in normal cells. PLA2R1 structure–function studies and the use of chemical inhibitors of sPLA2-related signaling pathways suggest that the effect of PLA2R1 is sPLA2-independent. Functional experiments demonstrate that PLA2R1 regulation of cell death is driven by a reactive oxygen species (ROS)-dependent mechanism. While screening for ROS-producing complexes involved in PLA2R1 biological responses, we identified a critical role for the mitochondrial electron transport chain in PLA2R1-induced ROS production and cell death. Taken together, this set of data provides evidence for an important role of PLA2R1 in controlling cancer cell death by influencing mitochondrial biology. 相似文献
5.
《Bioscience, biotechnology, and biochemistry》2013,77(4):567-571
Casein was conjugated with dextran and galactomannan in a controlled dry state at a relative humidity of 79% and at 60°C for 24 hr. The covalent attachment of polysaccharides to casein was confirmed by SDS-PAGE and HPLC. The emulsifying activity of the casein-dextran and casein-galactomannan conjugates was 1.5 times higher than that of casein. The emulsion stability of the casein-dextran and casein-galactomannan conjugates was 10 times higher than that of casein. The improvement in these emulsifying properties reached a steady state when the conjugation of casein with polysaccharide was done for 24 hr in a controlled dry state, suggesting the rapid formation of conjugates through a Maillard reaction in the case of casein. Compared to commercial emulsifiers, the casein-polysaccharide conjugates showed better emulsifying properties in acidic and high-salt concentration systems. 相似文献
6.
Geoffrey P Dobson 《BBA》2002,1553(3):261-267
Our aim was to estimate a number of bioenergetic parameters in the beating mouse, rat and guinea pig heart in situ and compare the values to those in hearts of mammals over a 2000-fold range in body mass. For the mouse, rat and guinea pig heart, we report a phosphorylation ratio of 1005±50 (n=16), 460±32 (n=10) and 330±22 (n=5) mM−1 and a free cytosolic [ADP] concentration of 13, 18 and 22 μM, respectively. When each parameter was plotted against body mass, they scaled closely to the quarter power (−0.28, r=0.99 and −0.23, r=0.97). A similar regression slope was found when the inverse of free [ADP] was plotted against absolute mitochondrial (slope=−0.26, r=0.99) and myofibrillar volumes (slope=−0.24, r=0.99). The similar slopes indicate that the ratio of absolute mitochondria and myofibrillar volumes in the healthy mammalian heart is a constant, and independent of body size. In conclusion, our study supports the hypothesis that the mammalian heart has a number of highly conserved thermodynamic and kinetic parameters that obey quarter-power laws linking the phosphorylation ratio, ATP turnover rates, free [ADP] and absolute mitochondrial volumes to body size. The results are discussed in terms of possible mechanisms and potential deviations from these laws in some disease states. 相似文献
7.
Richard A. Nakashima 《Journal of bioenergetics and biomembranes》1989,21(4):461-470
The outer mitochondrial membrane receptor for hexokinase binding has been identified as the VDAC protein, also known as mitochondrial porin. The ability of the receptor to bind hexokinase is inhibited by pretreatment with dicyclohexylcarbodiimide (DCCD). At low concentrations, DCCD inhibits hexokinase binding by covalently labeling the VDAC protein, with no apparent effect on VDAC channel-forming activity. The stoichiometry of [14C]-DCCD labeling is consistent with one to two high-affinity DCCD-binding sites per VDAC monomer. A comparison between the sequence of yeast VDAC and a conserved sequence found at DCCD-binding sites of several membrane proteins showed two sites where the yeast VDAC amino acid sequence appears to be very similar to the conserved DCCD-binding sequence. Both of these sites are located near the C-terminal end of yeast VDAC (residues 257–265 and 275–283). These results are consistent with a model in which the C-terminal end of VDAC is involved in binding to the N-terminal end of hexokinase. 相似文献
8.
Oxidation of γ-Hydroxybutyrate to Succinic Semialdehyde by a Mitochondrial Pyridine Nucleotide-Independent Enzyme 总被引:2,自引:0,他引:2
Elaine E. Kaufman Thomas Nelson David Miller Noam Stadlan 《Journal of neurochemistry》1988,51(4):1079-1084
An antibody that inhibits over 95% of the cytosolic NADP+-dependent gamma-hydroxybutyrate (GHB) dehydrogenase activity of either rat brain or kidney was found to inhibit only approximately 50% of the conversion of [1-14C]GHB to 14CO2 by rat kidney homogenate. A similar result was obtained with sodium valproate, a potent inhibitor of GHB dehydrogenase. The mitochondrial fraction from rat brain and kidney was found to catalyze the conversion of [1-14C]GHB to 14CO2. The dialyzed mitochondrial fraction also catalyzed the oxidation of GHB to succinic semialdehyde (SSA) in a reaction that did not require added NAD+ or NADP+ and which was not inhibited by sodium valproate. The enzyme from the mitochondrial fraction which converts GHB to SSA appears to be distinct from the NADP+-dependent cytosolic oxidoreductase which catalyzes this reaction. 相似文献
9.
Immunological identification of yeast SCO1 protein as a component of the inner mitochondrial membrane 总被引:4,自引:0,他引:4
Summary The SCO1 gene of Saccharomyces cerevisiae encodes a 30 kDa protein which is specifically required for a post-translational step in the accumulation of subunits 1 and 2 of cytochrome c oxidase (COXI and COXII). Antibodies directed against a -Gal::SCO1 fusion protein detect SCO1 in the mitochondrial fraction of yeast cells. The SCO1 protein is an integral membrane protein as shown by its resistance to alkaline extraction and by its solubilization properties upon treatment with detergents. Based on the results obtained by isopycnic sucrose gradient centrifugation and by digitonin treatment of mitochondria, SCO1 is a component of the inner mitochondrial membrane. Membrane localization is mediated by a stretch of 17 hydrophobic amino acids in the amino-terminal region of the protein. A truncated SCO1 derivative lacking this segment, is no longer bound to the membrane and simultaneously loses its biological function. The observation that membrane localization of SCO1 is affected in mitochondria of a rho
0 strain, hints at the possible involvement of mitochondrially coded components in ensuring proper membrane insertion. 相似文献
10.
Phenylarsine oxide induces the cyclosporin A-sensitive membrane permeability transition in rat liver mitochondria 总被引:2,自引:0,他引:2
Ewa Lenartowicz Paolo Bernardi Giovanni Felice Azzone 《Journal of bioenergetics and biomembranes》1991,23(4):679-688
This paper reports an investigation on the effects of the hydrophobic, bifunctional SH group reagent phenylarsine oxide (PhAsO) on mitochondrial membrane permeability. We show that PhAsO is a potent inducer of the mitochondrial permeability transition in a process which is sensitive to both the oxygen radical scavanger BHT and to cyclosporin A. The PhAsO-induced permeability transition is stimulated by Ca2+ but takes place also in the presence of EGTA in a process that maintains its sensitivity to BHT and cyclosporin A. Our findings suggest that, at variance from other known inducers of the permeability transition, PhAsO reacts directly with functional SH groups that are inaccessible to hydrophilic reagents in the absence of Ca2+. 相似文献