全文获取类型
收费全文 | 6109篇 |
免费 | 233篇 |
国内免费 | 220篇 |
出版年
2023年 | 39篇 |
2022年 | 51篇 |
2021年 | 66篇 |
2020年 | 95篇 |
2019年 | 131篇 |
2018年 | 135篇 |
2017年 | 97篇 |
2016年 | 130篇 |
2015年 | 143篇 |
2014年 | 329篇 |
2013年 | 493篇 |
2012年 | 203篇 |
2011年 | 309篇 |
2010年 | 211篇 |
2009年 | 305篇 |
2008年 | 319篇 |
2007年 | 346篇 |
2006年 | 288篇 |
2005年 | 270篇 |
2004年 | 267篇 |
2003年 | 223篇 |
2002年 | 186篇 |
2001年 | 131篇 |
2000年 | 121篇 |
1999年 | 129篇 |
1998年 | 124篇 |
1997年 | 115篇 |
1996年 | 100篇 |
1995年 | 99篇 |
1994年 | 100篇 |
1993年 | 101篇 |
1992年 | 75篇 |
1991年 | 70篇 |
1990年 | 59篇 |
1989年 | 49篇 |
1988年 | 63篇 |
1987年 | 63篇 |
1986年 | 41篇 |
1985年 | 71篇 |
1984年 | 56篇 |
1983年 | 51篇 |
1982年 | 80篇 |
1981年 | 52篇 |
1980年 | 36篇 |
1979年 | 32篇 |
1978年 | 13篇 |
1977年 | 24篇 |
1976年 | 16篇 |
1975年 | 14篇 |
1973年 | 13篇 |
排序方式: 共有6562条查询结果,搜索用时 62 毫秒
91.
92.
Cortical Cytochrome Oxidase Activity Is Reduced in Alzheimer's Disease 总被引:21,自引:5,他引:16
Abstract: A defect in energy metabolism may play a role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease. In the present study, we examined the activities of the enzymes that catalyze oxidative phosphorylation in frontal, temporal, parietal, and occipital cortex from Alzheimer's disease patients and age-matched controls. Complex I and complex II–III activities showed a small decrease in occipital cortex, but were unaffected in the other cortical areas. The most consistent change was a significant decrease of cytochrome oxidase (complex IV) activity of 25–30% in the four cortical regions examined. These results provide further evidence of a cytochrome oxidase defect in Alzheimer's disease postmortem brain tissue. A deficiency in this key energy-metabolizing enzyme could lead to a reduction in energy stores and thereby contribute to the neurodegenerative process. 相似文献
93.
D. James Morré 《Journal of bioenergetics and biomembranes》1994,26(4):421-433
An NADH oxidase activity of animal and plant plasma membrane is described that is stimulated by hormones and growth factors. In plasma membranes of cancer cells and tissues, the activity appears to be constitutively activated and no longer hormone responsive. With drugs that inhibit the activity, cells are unable to grow although growth inhibition may be more related to a failure of the cells to enlarge than to a direct inhibition of mitosis. The hormone-stimulated activity in plasma membranes of plants and the constitutively activated NADH oxidase in tumor cell plasma membranes is inhibited by thiol reagents whereas the basal activity is not. These findings point to a thiol involvement in the action of the activated form of the oxidase. NADH oxidase oxidation by Golgi apparatus of rat liver is inhibited by brefeldin A plus GDP. Brefeldin A is a macrolide antibiotic inhibitor of membrane trafficking. A model is presented where the NADH oxidase functions as a thiol-disulfide oxidoreductase activity involved in the formation and breakage of disulfide bonds. The thiol-disulfide interchange is postulated as being associated with physical membrane displacement as encountered in cell enlargement or in vesicle budding. The model, although speculative, does provide a basis for further experimentation to probe a potential function for this enzyme system which, under certain conditions, exhibits a hormone- and growth factor-stimulated oxidation of NADH. 相似文献
94.
Maria Luz Perez José Ramón Valverde Beatriz Batuecas Francisco Amat Roberto Marco Rafael Garesse 《Journal of molecular evolution》1994,38(2):156-168
From the cloned mitochondrial DNAs (mtDNAs) isolated from two bisexual species, one Mediterranean, Artemia salina, and one American, Artemia franciscana, and two parthenogenetic (diploid and tetraploid) strains of Artemia parthenogenetica collected in Spain, physical maps have been constructed and compared. They are extremely different among themselves, much more than the differences between Drosophila melanogaster and D. yakuba and in the same range of different mammalian species such as mouse/rat or man/cow. The nucleotide sequences of two regions of mtDNA encoding parts of the cytochrome c oxidase subunit I (COI) and cytochrome b (Cytb) genes have been determined in the two bisexual species and the two parthenogenetic strains. Comparisons of these sequences have revealed a high degree of divergence at the nucleotide level, averaging more than 15%, in agreement with the differences found in the physical maps. The majority of the nucleotide changes are silent and there is a strong bias toward transitions, with the CT substitutions being highly predominant. The evolutionary distance between the two Artemia parthenogenetica is high and there is no clear relationship with any of the bisexual species, including the one present nowadays in Spain. Using a combination of molecular (mtDNA) and morphological markers it is possible to conclude that all of these Artemia isolates should be actually considered as belonging to different species, even the two Artemia parthenogenetica diploidica and tetraploidica.On sabbatical leave from Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense de Madridearly Italian artemiologists to designate the Medi-Beatriz Batuecas died in an accident during the Christmas holy days of 1988 after she had initiated this workCorrespondence to: R. Garesse 相似文献
95.
PET1402, a nuclear gene required for proteolytic processing of cytochrome oxidase subunit 2 in yeast
Mathias Bauer Meinhardt Behrens Karlheinz Esser Georg Michaelis Elke Pratje 《Molecular & general genetics : MGG》1994,245(3):272-278
The nuclear mutation pet ts1402 prevents proteolytic processing of the precursor of cytochrome oxidase subunit 2 (cox2) in Saccharomyces cerevisiae. The structural gene PET1402 was isolated by genetic complementation of the temperature-sensitive mutation. DNA sequence analysis identified a 1206-bp open reading frame, which is located 215 by upstream of the PET122 gene. The DNA sequence of PET1402 predicts a hydrophobic, integral membrane protein with four transmembrane segments and a typical mitochondrial targeting sequence. Weak sequence similarity was found to two bacterial proteins of unknown function. Haploid cells containing a null allelle of PET1402 are respiratory deficient. 相似文献
96.
Probing protein-cofactor interactions in the terminal oxidases by second derivative spectroscopy: study of bacterial enzymes with cofactor substitutions and heme A model compounds. 下载免费PDF全文
J. S. Felsch M. P. Horvath S. Gursky M. R. Hobaugh P. N. Goudreau J. A. Fee W. T. Morgan S. J. Admiraal M. Ikeda-Saito T. Fujiwara et al. 《Protein science : a publication of the Protein Society》1994,3(11):2097-2103
Second derivative absorption spectra are reported for the aa3-cytochrome c oxidase from bovine cardiac mitochondria, the aa3-600 ubiquinol oxidase from Bacillus subtilis, the ba3-cytochrome c oxidase from Thermus thermophilis, and the aco-cytochrome c oxidase from Bacillus YN-2000. Together these enzymes provide a range of cofactor combinations that allow us to unequivocally identify the origin of the 450-nm absorption band of the terminal oxidases as the 6-coordinate low-spin heme, cytochrome a. The spectrum of the aco-cytochrome c oxidase further establishes that the split Soret band of cytochrome a, with features at 443 and 450 nm, is common to all forms of the enzyme containing ferrocytochrome a and does not depend on ligand occupancy at the other heme cofactor as previously suggested. To test the universality of this Soret band splitting for 6-coordinate low-spin heme A systems, we have reconstituted purified heme A with the apo forms of the heme binding proteins, hemopexin, histidine-proline-rich glycoprotein and the H64V/V68H double mutant of human myoglobin. All 3 proteins bound the heme A as a (bis)histidine complex, as judged by optical and resonance Raman spectroscopy. In the ferroheme A forms, none of these proteins displayed evidence of Soret band splitting. Heme A-(bis)imidazole in aqueous detergent solution likewise failed to display Soret band splitting. When the cyanide-inhibited mixed-valence form of the bovine enzyme was partially denatured by chemical or thermal means, the split Soret transition of cytochrome a collapsed into a single band at 443 nm.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
97.
In our previous experiments, evidence of free radical formation has been demonstrated in gerbil brain after kainic acid (KA) administration. In the present study, the mechanisms involved in KA-induced free radical formation and subsequent cell degeneration were investigated using high density cortical neuron cultures. A free radical trapping agent,a-phenyl-N-tert-butyl-nitrone (PBN), as well as the combined action of superoxide dismutase and catalase attenuated KA neurotoxic effect. Calpain-induced xanthine oxidase (XO) activation may play an important role in KA excitotoxicity since calpain inhibitor I as well as allopurinol, a selective XO inhibitor, significantly protected the cortical neurons from KA-induced cell death. However, XO activation may not be the only source producing free radicals, other free radical generating systems such as nitric oxide synphase may also play a role in KA insult. 相似文献
98.
Brian Duff Sloley 《Neurochemical research》1994,19(2):217-222
The conversion of 5-hydroxytryptamine to several potential metabolites was examined in the annelid earthworm (Lumbricus terrestris). 5-hydroxytryptamine and some related amines were found to be present in several tissues of the earthworm. Injection of 5-hydroxytryptamine into the body cavity of the earthworm resulted in the production of a -glutamyl conjugate of 5-hydroxytryptamine. Incubations of the anterior nerve cord of the earthworm resulted in the accumlation of considerable amounts of 5-hydroxytryptamine and -glutamyl 5-hydroxytryptamine in the incubation medium. The earthworm did not produce any N-acetyl 5-hydroxytryptamine and only very little 5-hydroxyindoleacetic acid. Experiments involving the injection of radiolabeled 5-hydroxytryptamine or coninjection of radiolabeled glutamic acid with unlabeled 5-hydroxytryptamine into the earthworm resulted in the production of radiolabeled -glutamyl 5-hydroxytryptamine. This work demonstrates that the enzymatic conversion of 5-HT in the earthworm is markedly different from that of vertebrates and insects. 相似文献
99.
Neal C. Robinson 《Journal of bioenergetics and biomembranes》1993,25(2):153-163
Bovine cytochromec oxidase usually contains 3–4 mol of tightly bound cardiolipin per cytochromeaa
3 complex. At least two of these cardiolipins are required for full electron transport activity. Without the tightly bound cardiolipin, cytochromec oxidase has only 40–50% of its original activity when assayed in detergents that support activity, e.g., dodecyl maltoside. By measuring the restoration of electron transport activity, functional binding constants for cardiolipin and a number of cardiolipin analogues have been evaluated (K
d,app=1 µM for cardiolipin). These binding constants agree reasonably well with direct measurement of the binding using [14C]-acetyl-cardiolipin (K
d
<0.1 µM) when the enzyme is solubilized with Triton X-100. These data are discussed in relationship to the wealth of data that is known about the association of cardiolipin with cytochromec oxidase and the other mitochrondrial electron transport complexes and transporters. 相似文献
100.
Robert A. Copeland 《Journal of bioenergetics and biomembranes》1993,25(2):93-102
The electronic transitions of the two heme groups of cytochromec oxidase have been resolved by application of second-derivative and cryogenic absorption spectroscopy. Both methods reveal a splitting of the ferrocytochromea Soret transition into two features at 443 and 450 nm. The relative intensity of the 450 nm feature appears to depend on the ligation state of cytochromea
3, the solution pH, and complex formation with cytochromec. The structural origin and mechanistic significance of this second Soret transition of cytochromea are discussed in terms of the electron transfer and proton translocation activities of the enzyme.Dedicated to the memory of James Carl Copeland. 相似文献