全文获取类型
收费全文 | 206篇 |
免费 | 13篇 |
专业分类
219篇 |
出版年
2021年 | 1篇 |
2015年 | 1篇 |
2014年 | 6篇 |
2013年 | 9篇 |
2012年 | 2篇 |
2011年 | 3篇 |
2010年 | 2篇 |
2009年 | 3篇 |
2008年 | 2篇 |
2007年 | 5篇 |
2006年 | 8篇 |
2005年 | 8篇 |
2004年 | 11篇 |
2003年 | 11篇 |
2002年 | 12篇 |
2001年 | 9篇 |
2000年 | 11篇 |
1999年 | 7篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 6篇 |
1991年 | 10篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 8篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 7篇 |
1972年 | 4篇 |
1971年 | 1篇 |
排序方式: 共有219条查询结果,搜索用时 0 毫秒
81.
The stalk connecting the F1 and F0 domains of ATP synthase visualized by electron microscopy of unstained specimens 总被引:2,自引:0,他引:2
E. coli F1F0 ATP synthase has been reconstituted into membranes and visualized by electron microscopy of unstained samples preserved in thin layers of amorphous ice. Unlike previous observations in negative stain, these specimens are not exposed to potentially denaturing or perturbing conditions, having been rapidly frozen from well-defined conditions in which the enzyme is fully active. The structures visualized in views normal to the lipid bilayer clearly show the presence of a narrow stalk approx. 45 A long, connecting the F1 to the membrane-embedded F0. 相似文献
82.
Alessandra Eleuteri Daniel C. Capaldi Douglas L. Cole Vasulinga T. Ravikumar 《Nucleosides, nucleotides & nucleic acids》2013,32(3):475-483
Abstract Use of fully protected trimeric phosphoramidite synthons in the synthesis of oligonucleotide phosphorothioate shows a substantial reduction (>85%) in (n-1)-mer content as compared to oligomers synthesized through coupling of standard phosphoramidite monomers. A 20-mer oligodeoxyribonucleotide phosphorothioate which is in phase I clinical trials was chosen as an example for the studies. 相似文献
83.
Baden KN Murray J Capaldi RA Guillemin K 《The Journal of biological chemistry》2007,282(48):34839-34849
Deficiency of cytochrome c oxidase (COX) is associated with significant pathology in humans. However, the consequences for organogenesis and early development are not well understood. We have investigated these issues using a zebrafish model. COX deficiency was induced using morpholinos to reduce expression of CoxVa, a structural subunit, and Surf1, an assembly factor, both of which impaired COX assembly. Reduction of COX activity to 50% resulted in developmental defects in endodermal tissue, cardiac function, and swimming behavior. Cellular investigations revealed different underlying mechanisms. Apoptosis was dramatically increased in the hindbrain and neural tube, and secondary motor neurons were absent or abnormal, explaining the motility defect. In contrast, the heart lacked apoptotic cells but showed increasingly poor performance over time, consistent with energy deficiency. The zebrafish model has revealed tissue-specific responses to COX deficiency and holds promise for discovery of new therapies to treat mitochondrial diseases in humans. 相似文献
84.
The subunit structure of ubiquinone-cytochrome c reductase (complex III) has been examined and eight different polypeptides have been identified. Apparent molecular weights for each have been obtained by one or more methods including polyacrylamide gel electrophoresis in sodium doecyl sulfate and in sodium dodecyl sulfate-8 M urea and by gel filtration in sodium dodecyl sulfate and in 6 M guanidine hydrochloride. Values obtained are as follows: I, 47 500; II, 45 500; III, 29 500; IV, 27 800; V, 24 800; VI, 13 900; VII, 10 700; VIII, 4 800-9 00. Individual polypeptides have been purified and the amino acid composition of several of these have been determined. At least one polypeptide, the apoprotein of cytochrome b, is hydrophobic in character and this is a mitochondrially synthesized component (B. Lorenz, W. Kleinow, and H. Weiss (1974), Hoppe-Seyler's Z. Physiol. Chem. 355, 300). Other polypeptides including the hemoprotein of cytochrome c1 are more hydrophilic in amino acid composition. 相似文献
85.
The rate of trypsin cleavage of the epsilon subunit of Escherichia coli F1F0 (ECF1F0) is shown to be ligand-dependent as measured by Western analysis using monoclonal antibodies. The cleavage of the epsilon subunit was rapid in the presence of ADP alone, ATP + EDTA, or AMP-PNP + Mg2+, but slow when Pi was added along with ADP + Mg2+ or when ATP + Mg2+ was added to generate ADP + Pi (+Mg2+) in the catalytic site. Trypsin treatment of ECF1Fo was also shown to increase enzymic activity on a time scale corresponding to that of the cleavage of the epsilon subunit, indicating that the epsilon subunit inhibits ATPase activity in ECF1Fo. The ligand-dependent conformational changes in the epsilon subunit were also examined in cross-linking experiments using the water-soluble carbodiimide 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide (EDC). In the presence of ATP + Mg2+ or ADP + Pi + Mg2+, the epsilon subunit cross-linked product was much reduced. Prior reaction of ECF1Fo with dicyclohexylcarbodiimide (DCCD), under conditions in which only the Fo part was modified, blocked the conformational changes induced by ligand binding. When the enzyme complex was reacted with DCCD in ATP + EDTA, the cleavage of the epsilon subunit was rapid and yield of cross-linking of beta to epsilon subunit low, whether trypsin cleavage was conducted in ATP + EDTA or ATP + Mg2+. When enzyme was reacted with DCCD in ATP + Mg2+, cleavage of the epsilon subunit was slow and yield of cross-linking of beta to epsilon high, under all nucleotide conditions for proteolysis.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
86.
The isolated and membrane-bound forms of the adenosinetriphosphatase of Escherichia coli (ECF1 and ECF1F0, respectively) have been reacted with two lysine-specific reagents, sodium hexadecyl 4-[3H]formylphenyl phosphate (HFPP) and sodium methyl 4-[3H]formylphenyl phosphate (MFPP), and with the photoreactive reagent 1,2-[3H]dipalmitoyl-sn-glycerol 3-[[[(4-azido-2-nitrophenyl)amino]ethyl]-phosphate] (arylazidoPE). HFPP and arylazidoPE are amphipathic molecules, inserting by their hexadecyl moieties (one and two chains, respectively) into the lipid bilayer, with the reactive groups intercalated among the phospholipid head groups. MFPP is the water-soluble analogue of HFPP. The labeling patterns of ECF1F0 obtained with HFPP and arylazidoPE were very similar; in both cases the a and b subunits of the F0 part were the most heavily labeled polypeptides of the complex. Models of subunit a, arranged in six transmembrane helices, place most of the lysines in the head-group region, available for reaction with HFPP. Subunits alpha and beta of the ECF1 part were very poorly labeled in comparison to the a and b subunits, together incorporating only 4% as much HFPP and 7.5% as much arylazidoPE as the two F0 subunits together on a protein mass basis. Trypsin cleavage studies localized any labeling of the alpha subunit by arylazidoPE to the N-terminal 15 residues of this polypeptide. When MFPP was used, the alpha and beta subunits were very much more reacted than the F0 subunits. This implies that most of the mass of the alpha and beta subunits in ECF1F0 is above the membrane and not in contact with the bilayer surface.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
87.
Schilling B Bharath M M S Row RH Murray J Cusack MP Capaldi RA Freed CR Prasad KN Andersen JK Gibson BW 《Molecular & cellular proteomics : MCP》2005,4(1):84-96
Oxidative stress and mitochondrial dysfunction signify important biochemical events associated with the loss of dopaminergic neurons in Parkinson's disease (PD). Studies using in vitro and in vivo PD models or tissues from diseased patients have demonstrated a selective inhibition of mitochondrial NADH dehydrogenase (Complex I of the OXPHOS electron transport chain) that affects normal mitochondrial physiology leading to neuronal death. In an earlier study, we demonstrated that oxidative stress due to glutathione depletion in dopaminergic cells, a hallmark of PD, leads to Complex I inhibition via cysteine thiol oxidation (Jha et al. (2000) J. Biol. Chem. 275, 26096-26101). Complex I is a approximately 980-kDa multimeric enzyme spanning the inner mitochondrial membrane comprising at least 45 protein subunits. As a prerequisite to investigating modifications to Complex I using a rodent disease model for PD, we developed two independent rapid and mild isolation procedures based on sucrose gradient fractionation and immunoprecipitation to isolate Complex I from mouse brain and a cultured rat mesencephalic dopaminergic neuronal cell line. Both protocols are capable of purifying Complex I from small amounts of rodent tissue and cell cultures. Blue Native gel electrophoresis, one-dimensional and two-dimensional SDS-PAGE were employed to assess the purity and composition of isolated Complex I followed by extensive mass spectrometric characterization. Altogether, 41 of 45 rodent Complex I subunits achieved MS/MS sequence coverage. To our knowledge, this study provides the first detailed mass spectrometric analysis of neuronal Complex I proteins and provides a means to investigate the role of cysteine oxidation and other posttranslational modifications in pathologies associated with mitochondrial dysfunction. 相似文献
88.
89.
The C-terminal extrahelical peptide of type I collagen and its role in fibrillogenesis in vitro: effects of ethylurea 总被引:1,自引:0,他引:1
Ethylurea was used to weaken hydrophobic interactions during collagen fibrillogenesis in vitro. Intact and enzyme-digested type I collagen was studied. In all preparations, ethylurea decreased the extent and rate of fibril formation, inhibition being greatest in the enzyme-digested collagens. With intact collagen (and probably also with carboxypeptidasedigested collagen), there was no evidence the ethylurea altered the mechanism of fibril growth; in pepsin-digested collagen, however, the growth mechanism was altered by ethylurea, possibly reflecting a conformational change of the “hydrophobic cluster” in the C-terminal peptide. Such a structural change could occur in a hydrophobic environment once the distal portion of the C-terminal peptide (presumed to be essential for its structural stability) is removed by pepsin. The results further emphasize the importance of hydrophobic interactions in collagen fibril nucleation and growth in vitro. 相似文献
90.