全文获取类型
收费全文 | 873篇 |
免费 | 70篇 |
国内免费 | 8篇 |
专业分类
951篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 9篇 |
2021年 | 24篇 |
2020年 | 15篇 |
2019年 | 22篇 |
2018年 | 39篇 |
2017年 | 31篇 |
2016年 | 30篇 |
2015年 | 42篇 |
2014年 | 67篇 |
2013年 | 51篇 |
2012年 | 78篇 |
2011年 | 97篇 |
2010年 | 48篇 |
2009年 | 33篇 |
2008年 | 60篇 |
2007年 | 58篇 |
2006年 | 48篇 |
2005年 | 37篇 |
2004年 | 33篇 |
2003年 | 25篇 |
2002年 | 29篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 9篇 |
1997年 | 1篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 6篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1962年 | 1篇 |
排序方式: 共有951条查询结果,搜索用时 15 毫秒
11.
Sorokin Vladimir V. Pshenichnikova Anna B. Kalenov Sergei V. Suyasov Nikolay A. Skladnev Dmitry A. 《Biological trace element research》2020,193(2):564-573
Biological Trace Element Research - Metal nanoparticles synthesized by green methods with the use of microorganisms are currently one of the most closely studied types of nanomaterials. It has... 相似文献
12.
Relationship between the structure of amphiphilic copolymers and their ability to disturb lipid bilayers 总被引:2,自引:0,他引:2
Demina T Grozdova I Krylova O Zhirnov A Istratov V Frey H Kautz H Melik-Nubarov N 《Biochemistry》2005,44(10):4042-4054
Nonionic amphiphiles and particularly block copolymers of ethylene oxide and propylene oxide (Pluronics) cause pronounced chemosensitization of tumor cells that exhibit multiple resistance to antineoplastic drugs. This effect is due to inhibition of P-glycoprotein (P-gp) responsible for drug efflux. It was suggested that the inhibition of P-gp might be due to changes in its lipid surrounding. Indeed, high dependence of P-gp activity on the membrane microviscosity was demonstrated [Regev et al. (1999) Eur. J. Biochem. 259, 18-24], suggesting that the ability of Pluronics to affect the P-gp activity is mediated by their effect on the membrane structure. We have found recently that adsorption of Pluronics on lipid bilayers induced considerable disturbance of the lipid packing [Krylova et al. (2003) Chemistry 9, 3930-3936]. In the present paper, we studied 19 amphiphilic copolymers, including newly synthesized hyperbranched polyglycerols, Pluronic and Brij surfactants, for their ability to accelerate flip-flop and permeation of antitumor drug doxorubicin (DOX) in liposomes. It was found that not only bulk hydrophobicity but also the chemical microstructure of the copolymer determines its membrane disturbing ability. Copolymers containing polypropylene oxide caused higher acceleration of flip-flop and DOX permeation than polysurfactants containing aliphatic chains. The effects of copolymers containing hyperbranched polyglycerol "corona" were more pronounced, as compared to the copolymers with linear poly(ethylene oxide) chains, indicating that a bulky hydrophilic block induces additional disturbances in the lipid bilayer. A good correlation between the copolymer flippase activity and a linear combination of copolymer bulk hydrophobicity and the van der Waals volume of its hydrophobic block was found. The relationship between the structure of a copolymer and its ability to disturb lipid membranes presented in this paper may be useful for the design of novel amphiphilic copolymers capable of affecting the activity of membrane transporters in living cells. 相似文献
13.
Minkov Nikolay Lehmann Annekatrin Finkbeiner Matthias 《The International Journal of Life Cycle Assessment》2020,25(3):508-522
The International Journal of Life Cycle Assessment - Since 2013, the European Commission (EC) is developing and testing the Product Environmental Footprint (PEF)—a product evaluation method,... 相似文献
14.
Nikolay?V.?MaximovichEmail author Alexandra?V.?Guerassimova 《Helgoland Marine Research》2003,57(2):91-99
Dynamics of Mya arenaria beds in two bights of the Chupa Inlet (Kandalaksha Bay, White Sea) were studied on a long-term basis. Observations were carried
out at 1– to 3-year intervals from 1979 up to 1999. The studied soft-shell clam beds were characterised by a substantial instability
of age structure. Since 1988, only one year-class has dominated in the beds while other generations have been scarce and recruitment
was not observed. This pattern of Mya bed dynamics was related neither to interannual environmental changes nor to differential reproduction success or predation
effects in the benthic assemblages. Favourable conditions for spat formation in 1988 (low abundance of other M. arenaria generations), as well as for juvenile survival during the following winter, resulted in high abundance of juveniles in both
investigated locations in 1989. The mortality rate (μ) in this 1988 generation varied throughout the period of investigation and was related to age. The mortality level decreased
for the first 2–4 years of the life cycle, then stabilised for the next 3–4 years, and eventually increased in subsequent
years. Overall μ values ranged from 0 to 1.68 year–1. The oldest specimens observed were 17 years old and had a maximum shell length of 79 mm. Significant differences in average
growth rates were observed between molluscs of different locations.
Communicated by H.-D. Franke 相似文献
15.
Olia V. Karnachuk Nikolay V. Pimenov Sandjar K. Yusupov Yulia A. Frank Yulia A. Frank Anna H. Kaksonen 《Geomicrobiology journal》2013,30(1-2):11-25
Abstract The purpose of this study was to characterize the distribution and activity of sulfate-reducing bacteria in tailings and sediments impacted by effluents from mining and smelting operations in the Norilsk area in northern Siberia. The Norilsk mining complex involves three smelter operations, a hydrometallurgical plant, and extensive tailings areas located in the permafrost zone. Sulfate reduction rates measured with a 35SO4 2? tracer technique under various in-situ conditions ranged from 0.05 to 30 nmol S cm?3 day?1. Acetate and glucose addition greatly stimulated sulfate reduction, whereas lactate had less effect. The most pronounced stimulation of sulfate reduction (6.5-fold) was observed with phosphate amendment. Most-probable-number (MPN) counts of sulfate-reducing bacteria in media with glucose, ethanol, lactate, and acetate as electron donors were generally highest at around 107 cells ml?1. The actual MPN counts varied with the sample, electron donor, and incubation conditions (pH 7.2 vs. pH 3.5; 28°C vs. 4°C). Enrichment cultures of sulfate-reducing bacteria were established from a sample that showed the highest rate of sulfate reduction. After multiple serial transfers, the dominant sulfate-reducers were identified by fluorescence in situ hybridization using genus and group-specific 16S rRNA-targeted oligonucleotide probes. Desulfobulbus spp. prevailed in ethanol and lactate enrichments and the Desulfosarcina-Desulfococcus group dominated in acetate and benzoate enrichments. Psychrophilic Desulfotalea-Desulfofustis and moderately psychrophilic Desulforhopalus spp. were identified in enrichments incubated at 4°C, but they were also found in mesophilic enrichments. 相似文献
16.
Dygalo NN Kalinina TS Bulygina VV Shishkina GT 《Cellular and molecular neurobiology》2012,32(5):767-776
Clinical observations and the results of animal studies have implicated changes in neuronal survival and plasticity in both the etiology of mood disorders, especially stress-induced depression, and anti-depressant drug action. Stress may predispose individuals toward depression through down-regulation of neurogenesis and an increase in apoptosis in the brain. Substantial individual differences in vulnerability to stress are evident in humans and were found in experimental animals. Recent studies revealed an association between the brain anti-apoptotic protein B cell lymphoma like X, long variant (Bcl-xL) expression and individual differences in behavioral vulnerability to stress. The ability to increase Bcl-xL gene expression in the hippocampus in response to stress may be an important factor for determining the resistance to the development of stress-induced depression. Treatment with anti-depressant drugs may change Bcl-xL response properties. In the rat brainstem, expression of this anti-apoptotic gene becomes sensitive to swim stress during the long-term fluoxetine treatment, an effect that appeared concomitantly with the anti-depressant-like action of the drug in the forced swim test, suggesting that Bcl-xL may be a new target for depression therapy. The processes and pathways linking stress stimuli to behavior via intracellular anti-apoptotic protein are discussed here in the context of Bcl-xL functions in the mechanisms of individual differences in behavioral resilience to stress and anti-depressant-induced effects on the behavioral despair. 相似文献
17.
Valentina M. Drozd Vladimir A. Saenko Alina V. Brenner Vladimir Drozdovitch Vasilii I. Pashkevich Anatoliy V. Kudelsky Yuri E. Demidchik Igor Branovan Nikolay Shiglik Tatiana I. Rogounovitch Shunichi Yamashita Johannes Biko Christoph Reiners 《PloS one》2015,10(9)
One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (131I) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the 131I-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer. 相似文献
18.
A hidden aggregation‐prone structure in the heart of hypoxia inducible factor prolyl hydroxylase 下载免费PDF全文
Hamid Hadi‐Alijanvand Elizabeth A. Proctor Feng Ding Nikolay V. Dokholyan Ali A. Moosavi‐Movahedi 《Proteins》2016,84(5):611-623
Prolyl hydroxylase domain‐containing protein 2 (PHD2), as one of the most important regulators of angiogenesis and metastasis of cancer cells, is a promising target for cancer therapy drug design. Progressive studies imply that abnormality in PHD2 function may be due to misfolding. Therefore, study of the PHD2 unfolding pathway paves the way for a better understanding of the influence of PHD2 mutations and cancer cell metabolites on the protein folding pathway. We study the unfolding of the PHD2 catalytic domain using differential scanning calorimetry (DSC), fluorescence spectroscopy, and discrete molecular dynamics simulations (DMD). Using computational and experimental techniques, we find that PHD2 undergoes four transitions along the thermal unfolding pathway. To illustrate PHD2 unfolding events in atomic detail, we utilize DMD simulations. Analysis of computational results indicates an intermediate species in the PHD2 unfolding pathway that may enhance aggregation propensity, explaining mutation‐independent PHD2 malfunction. Proteins 2016; 84:611–623. © 2016 Wiley Periodicals, Inc. 相似文献
19.
The ability of hydrogenases isolated from Thiocapsa roseopersicina and Lamprobacter modestohalophilus to reduce metal ions and oxidize metals has been studied. Hydrogenases from both phototrophic bacteria oxidized metallic Fe, Cd, Zn and Ni into their ionic forms with simultaneous evolution of molecular hydrogen. The metal oxidation rate decreased in the series Zn>Fe>Cd>Ni and depended on the pH. The presence of methyl viologen in the reaction system accelerated this process. T. roseopersicina and L. modestohalophilus cells and their hydrogenases reduced Ni(II), Pt(IV), Pd(II) or Ru(III) to their metallic forms under H2 atmosphere. These results suggest that metals or metal ions can serve as electron donors or acceptors for hydrogenases from phototrophic bacteria. 相似文献
20.
Rainer Nikolay Renate Schloemer Sabine Schmidt Silke Mueller Anja Heubach Elke Deuerling 《Nucleic acids research》2014,42(12):e100
While the structure of mature ribosomes is analyzed in atomic detail considerably less is known about their assembly process in living cells. This is mainly due to technical and conceptual hurdles. To analyze ribosome assembly in vivo, we designed and engineered an Escherichiacoli strain—using chromosomal gene knock-in techniques—that harbors large and small ribosomal subunits labeled with the fluorescent proteins EGFP and mCherry, respectively. A thorough characterization of this reporter strain revealed that its growth properties and translation apparatus were wild-type like. Alterations in the ratio of EGFP over mCherry fluorescence are supposed to indicate ribosome assembly defects. To provide proof of principle, subunit specific assembly defects were provoked and could be identified by both manual and fully automated fluorometric in vivo assays. This is to our knowledge the first methodology that directly detects ribosome assembly defects in vivo in a high-throughput compatible format. Screening of knock-out collections and small molecule libraries will allow identification of new ribosome assembly factors and possible inhibitors. 相似文献