全文获取类型
收费全文 | 2745篇 |
免费 | 237篇 |
国内免费 | 2篇 |
出版年
2023年 | 7篇 |
2022年 | 32篇 |
2021年 | 86篇 |
2020年 | 45篇 |
2019年 | 66篇 |
2018年 | 76篇 |
2017年 | 86篇 |
2016年 | 88篇 |
2015年 | 157篇 |
2014年 | 157篇 |
2013年 | 216篇 |
2012年 | 199篇 |
2011年 | 212篇 |
2010年 | 132篇 |
2009年 | 128篇 |
2008年 | 178篇 |
2007年 | 212篇 |
2006年 | 183篇 |
2005年 | 158篇 |
2004年 | 153篇 |
2003年 | 116篇 |
2002年 | 132篇 |
2001年 | 16篇 |
2000年 | 9篇 |
1999年 | 13篇 |
1998年 | 24篇 |
1997年 | 18篇 |
1996年 | 10篇 |
1995年 | 6篇 |
1994年 | 9篇 |
1993年 | 13篇 |
1992年 | 8篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1984年 | 1篇 |
1983年 | 4篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1975年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有2984条查询结果,搜索用时 15 毫秒
131.
Brautaset T Borgos SE Sletta H Ellingsen TE Zotchev SB 《The Journal of biological chemistry》2003,278(17):14913-14919
The loading module for the nystatin polyketide synthase (PKS) in Streptomyces noursei is represented by the NysA protein composed of a ketosynthase (KS(S)), acyltransferase, dehydratase, and an acyl carrier protein. The absolute requirement of this protein for initiation of nystatin biosynthesis was demonstrated by the in-frame deletion of the nysA gene in S. noursei. The role of the NysA KS(S) domain, however, remained unclear, since no data on the significance of the "active site" serine (Ser-170) residue in the loading modules of type I PKSs were available. Site-specific mutagenesis of Ser-170 both in the wild-type NysA and in the hybrid loading module containing malonyl-specific acyltransferase domain from the extender module had no effect on nystatin biosynthesis. A second mutation (S413N) of the NysA KS(S) domain was discovered that completely abolished the ability of the hybrids to restore nystatin biosynthesis, presumably by affecting the ability of the resulting proteins to catalyze the required substrate decarboxylation. In contrast, NysA and its Ser-170 mutants bearing the same S413N mutation were able to restore nystatin production to significant levels, probably by using acetyl-CoA as a starter unit. Together, these data suggest that the KS(S) domain of NysA differs from the KS(Q) domains found in the loading modules of several PKS type I systems in that the active site residue is not significant for its activity. 相似文献
132.
Cytochrome c is transformed from anti- to pro-oxidant when interacting with truncated oncoprotein prothymosin alpha 总被引:2,自引:0,他引:2
Markova OV Evstafieva AG Mansurova SE Moussine SS Palamarchuk LA Pereverzev MO Vartapetian AB Skulachev VP 《Biochimica et biophysica acta》2003,1557(1-3):109-117
Many apoptotic signals are known to induce release to cytosol of cytochrome c, a small mitochondrial protein with positively charged amino acid residues dominating over negatively charged ones. On the other hand, in this group, it was shown that prothymosin alpha (PT), a small nuclear protein where 53 of 109 amino acid residues are negatively charged, is truncated to form a protein of 99 amino acid residues which accumulates in cytosol during apoptosis [FEBS Lett. 467 (2000) 150]. It was suggested that positively charged cytochrome c and negatively charged truncated prothymosin alpha (tPT), when meeting in cytosol, can interact with each other. In this paper, such an interaction is shown. (1) Formation of cytochrome cz.ccirf;tPT complex is demonstrated by a blot-overlay assay. (2) Analytical centrifugation of solution containing cytochrome c and tPT reveals formation of complexes of molecular masses higher than those of these proteins. The masses increase when the cytochrome c/tPT ratio increases. High concentration of KCl prevents the complex formation. (3) In the complexes formed, cytochrome c becomes autoxidizable; its reduction by superoxide or ascorbate as well as its operation as electron carrier between the outer and inner mitochondrial membranes appear to be inhibited. (4) tPT inhibits cytochrome c oxidation by H(2)O(2), catalyzed by peroxidase. Thus, tPT abolishes all antioxidant functions of cytochrome c which, in the presence of tPT, becomes in fact a pro-oxidant. A possible role of tPT in the development of reactive oxygen species- and cytochrome c-mediated apoptosis is discussed. 相似文献
133.
Origin and diffusion of mtDNA haplogroup X 总被引:10,自引:0,他引:10
Reidla M Kivisild T Metspalu E Kaldma K Tambets K Tolk HV Parik J Loogväli EL Derenko M Malyarchuk B Bermisheva M Zhadanov S Pennarun E Gubina M Golubenko M Damba L Fedorova S Gusar V Grechanina E Mikerezi I Moisan JP Chaventré A Khusnutdinova E Osipova L Stepanov V Voevoda M Achilli A Rengo C Rickards O De Stefano GF Papiha S Beckman L Janicijevic B Rudan P Anagnou N Michalodimitrakis E Koziel S Usanga E Geberhiwot T Herrnstadt C Howell N Torroni A Villems R 《American journal of human genetics》2003,73(5):1178-1190
A maximum parsimony tree of 21 complete mitochondrial DNA (mtDNA) sequences belonging to haplogroup X and the survey of the haplogroup-associated polymorphisms in 13,589 mtDNAs from Eurasia and Africa revealed that haplogroup X is subdivided into two major branches, here defined as “X1” and “X2.” The first is restricted to the populations of North and East Africa and the Near East, whereas X2 encompasses all X mtDNAs from Europe, western and Central Asia, Siberia, and the great majority of the Near East, as well as some North African samples. Subhaplogroup X1 diversity indicates an early coalescence time, whereas X2 has apparently undergone a more recent population expansion in Eurasia, most likely around or after the last glacial maximum. It is notable that X2 includes the two complete Native American X sequences that constitute the distinctive X2a clade, a clade that lacks close relatives in the entire Old World, including Siberia. The position of X2a in the phylogenetic tree suggests an early split from the other X2 clades, likely at the very beginning of their expansion and spread from the Near East. 相似文献
134.
Jung C Kozin SA Canny B Chervin JC Hoa GH 《Biochemical and biophysical research communications》2003,312(1):197-203
The effect of the hydrostatic pressure on the CO ligand stretch vibration in cytochrome P450cam-CO bound with various substrates is studied by FTIR. The vibration frequency is linearily shifted to lower values with increasing pressure. The slope of the shift gives the isothermal compressibility of the heme pocket and is found to be related to the high-spin state content in an opposite direction to that previously observed from the pressure-induced shift of the Soret band. This opposite behaviour is explained by the dual effect of heme pocket water molecules both on the CO ligand and on electrostatic potentials produced by the protein at the distal side. The latter effect disturbs ligand-distal side contacts which are needed for a specific proton transfer in oxygen activation when dioxygen is the ligand. Their loss results in uncoupled H(2)O(2) formation. 相似文献
135.
Lavrenov SN Korolev AM Reznikova MI Sosnov AV Preobrazhenskaya MN 《Carbohydrate research》2003,338(2):143-152
Alkaline degradation of the ascorbigen 2-C-[(indol-3-yl)methyl]-alpha-L-xylo-hex-3-ulofuranosono-1,4-lactone (1a) led to a mixture of 1-deoxy-1-(indol-3-yl)-L-sorbose (2a) and 1-deoxy-1-(indol-3-yl)-L-tagatose (3a). The mixture of diastereomeric ketoses underwent acetylation and pyranose ring opening under the action of acetic anhydride in pyridine in the presence of 4-dimethylaminopyridine (DMAP) with the formation of a mixture of (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-xylo-hex-1-enitol (4a) and (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-lyxo-hex-1-enitol (5a), which were separated chromatographically. Deacetylation of 4a or 5a afforded cyclised tetrols, tosylation of which in admixture resulted in 1-deoxy-1-(indol-3-yl)-3,5-di-O-tosyl-alpha-L-sorbopyranose (12a) and 1-deoxy-1-(indol-3-yl)-4,5-di-O-tosyl-alpha-L-tagatopyranose (13a). Under alkaline conditions 13a readily formed 2-hydroxy-4-hydroxymethyl-3-(indol-3-yl)cyclopenten-2-one (15a) in 90% yield. Similar transformations were performed for N-methyl- and N-methoxyindole derivatives. 相似文献
136.
Necrosis: a specific form of programmed cell death? 总被引:17,自引:0,他引:17
For a long time necrosis was considered as an alternative to programmed cell death, apoptosis. Indeed, necrosis has distinct morphological features and it is accompanied by rapid permeabilization of plasma membrane. However, recent data indicate that, in contrast to necrosis caused by very extreme conditions, there are many examples when this form of cell death may be a normal physiological and regulated (programmed) event. Various stimuli (e.g., cytokines, ischemia, heat, irradiation, pathogens) can cause both apoptosis and necrosis in the same cell population. Furthermore, signaling pathways, such as death receptors, kinase cascades, and mitochondria, participate in both processes, and by modulating these pathways, it is possible to switch between apoptosis and necrosis. Moreover, antiapoptotic mechanisms (e.g., Bcl-2/Bcl-x proteins, heat shock proteins) are equally effective in protection against apoptosis and necrosis. Therefore, necrosis, along with apoptosis, appears to be a specific form of execution phase of programmed cell death, and there are several examples of necrosis during embryogenesis, a normal tissue renewal, and immune response. However, the consequences of necrotic and apoptotic cell death for a whole organism are quite different. In the case of necrosis, cytosolic constituents that spill into extracellular space through damaged plasma membrane may provoke inflammatory response; during apoptosis these products are safely isolated by membranes and then are consumed by macrophages. The inflammatory response caused by necrosis, however, may have obvious adaptive significance (i.e., emergence of a strong immune response) under some pathological conditions (such as cancer and infection). On the other hand, disturbance of a fine balance between necrosis and apoptosis may be a key element in development of some diseases. 相似文献
137.
Protein import into mitochondria is inhibited by protons (IC(50) pH 6.5). The channels of the import machinery were examined to further investigate this pH dependence. TOM and TIM23 are the protein translocation channels of the mitochondrial outer and inner membranes, respectively, and their single channel behaviors at various pHs were determined using patch-clamp techniques. While not identical, increasing H(+) concentration decreases the open probability of both TIM23 and TOM channels. The pattern of the pH dependences of protein import and channel properties suggests TIM23 open probability can limit import of nuclear-encoded proteins into the matrix of yeast mitochondria. 相似文献
138.
Valery N Urakov Igor A Valouev Eugeny I Lewitin Sergey V Paushkin Vyacheslav S Kosorukov Vitaly V Kushnirov Vladimir N Smirnov Michael D Ter-Avanesyan 《BMC molecular biology》2001,2(1):9-10
Background
Termination of translation in eukaryotes is controlled by two interacting polypeptide chain release factors, eRFl and eRF3. eRFl recognizes nonsense codons UAA, UAG and UGA, while eRF3 stimulates polypeptide release from the ribosome in a GTP- and eRFl – dependent manner. Recent studies has shown that proteins interacting with these release factors can modulate the efficiency of nonsense codon readthrough.Results
We have isolated a nonessential yeast gene, which causes suppression of nonsense mutations, being in a multicopy state. This gene encodes a protein designated Itt1p, possessing a zinc finger domain characteristic of the TRIAD proteins of higher eukaryotes. Overexpression of Itt1p decreases the efficiency of translation termination, resulting in the readthrough of all three types of nonsense codons. Itt1p interacts in vitro with both eRFl and eRF3. Overexpression of eRFl, but not of eRF3, abolishes the nonsense suppressor effect of overexpressed Itt1p.Conclusions
The data obtained demonstrate that Itt1p can modulate the efficiency of translation termination in yeast. This protein possesses a zinc finger domain characteristic of the TRIAD proteins of higher eukaryotes, and this is a first observation of such protein being involved in translation. 相似文献139.
VEGF-induced mobilization of caveolae and increase in permeability of endothelial cells 总被引:10,自引:0,他引:10
Chen J Braet F Brodsky S Weinstein T Romanov V Noiri E Goligorsky MS 《American journal of physiology. Cell physiology》2002,282(5):C1053-C1063
Glomerular epithelial cells (GEC) are aknown site of vascular endothelial growth factor (VEGF) production. Weestablished immortalized rat GEC, which retained the ability to produceVEGF. The isoforms expressed by GEC were defined as VEGF-205, -188, -120, and -164. The electrical resistance of endothelial cells culturedon GEC-conditioned matrix, an indicator of the permeability ofmonolayers to solutes, was significantly increased by the treatment with the neutralizing polyclonal antibodies to VEGF and decreased byVEGF-165. Transfection of endothelial cells with green fluorescence protein-caveolin construct and intravital confocal microscopy showedthat VEGF results in a rapid appearance of transcellular elongatedstructures decorated with caveolin. Transmission electron microscopy ofendothelial cells showed that caveolae undergo rapid internalizationand fusion 30 min after application of VEGF-165. Later (36 h),endothelial cells pretreated with VEGF developed fenestrae and showed adecrease in electrical resistance. Immunoelectron microscopy ofglomeruli confirmed VEGF localization to podocytes and in the basementmembrane. In summary, immortalized GEC retain the ability to synthesizeVEGF. Matrix-deposited and soluble VEGF leads to the enhancement ofcaveolae expression, their fission and fusion, formation of elongatedcaveolin-decorated structures, and eventual formation of fenestrae,both responsible for the increase in endothelial permeability. 相似文献
140.
Mainelis G Górny RL Reponen T Trunov M Grinshpun SA Baron P Yadav J Willeke K 《Biotechnology and bioengineering》2002,79(2):229-241
In this study, the effects of the electric charges and fields on the viability of airborne microorganisms were investigated. The electric charges of different magnitude and polarity were imparted on airborne microbial cells by a means of induction charging. The airborne microorganisms carrying different electric charge levels were then extracted by an electric mobility analyzer and collected using a microbial sampler. It was found that the viability of Pseudomonas fluorescens bacteria, used as a model for sensitive bacteria, carrying a net charge from 4100 negative to 30 positive elementary charges ranged between 40% and 60%; the viability of the cells carrying >2700 positive charges was below 1.5%. In contrast, the viability of the stress-resistant spores of Bacillus subtilis var. niger (used as simulant of anthrax-causing Bacillus anthracis spores when testing bioaerosol sensors in various studies), was not affected by the amount of electric charges on the spores. Because bacterial cells depend on their membrane potential for basic metabolic activities, drastic changes occurring in the membrane potential during aerosolization and the local electric fields induced by the imposed charges appeared to affect the sensitive cells' viability. These findings facilitate applications of electric charging for environmental control purposes involving sterilization of bacterial cells by imposing high electric charges on them. The findings from this study can also be used in the development of new bioaerosol sampling methods based on electrostatic principles. 相似文献