全文获取类型
收费全文 | 5863篇 |
免费 | 408篇 |
国内免费 | 9篇 |
专业分类
6280篇 |
出版年
2023年 | 19篇 |
2022年 | 53篇 |
2021年 | 115篇 |
2020年 | 60篇 |
2019年 | 98篇 |
2018年 | 136篇 |
2017年 | 113篇 |
2016年 | 134篇 |
2015年 | 257篇 |
2014年 | 251篇 |
2013年 | 375篇 |
2012年 | 459篇 |
2011年 | 502篇 |
2010年 | 288篇 |
2009年 | 261篇 |
2008年 | 409篇 |
2007年 | 394篇 |
2006年 | 403篇 |
2005年 | 349篇 |
2004年 | 330篇 |
2003年 | 304篇 |
2002年 | 300篇 |
2001年 | 44篇 |
2000年 | 39篇 |
1999年 | 61篇 |
1998年 | 96篇 |
1997年 | 30篇 |
1996年 | 49篇 |
1995年 | 36篇 |
1994年 | 31篇 |
1993年 | 31篇 |
1992年 | 31篇 |
1991年 | 19篇 |
1990年 | 19篇 |
1989年 | 13篇 |
1988年 | 10篇 |
1987年 | 5篇 |
1986年 | 8篇 |
1985年 | 9篇 |
1984年 | 12篇 |
1983年 | 7篇 |
1982年 | 22篇 |
1981年 | 12篇 |
1980年 | 10篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 9篇 |
1976年 | 7篇 |
1975年 | 6篇 |
1974年 | 7篇 |
排序方式: 共有6280条查询结果,搜索用时 15 毫秒
951.
Yun Kang Vladimir V. Lunin Tatiana Skarina Alexei Savchenko Michael J. Schurr Tung T. Hoang 《Molecular microbiology》2009,73(1):120-136
The Pseudomonas aeruginosa PsrA autorepressor has dual roles as a repressor of the fadBA5 β-oxidation operon and an activator of the stationary-phase sigma factor rpoS and exsCEBA operon of the type III secretion system (TTSS). Previously, we demonstrated that the repression of the fadBA5 operon by PsrA is relieved by long-chain fatty acids (LCFAs). However, the signal affecting the activation of rpoS and exsC via PsrA is unknown. In this study, microarray and gene fusion data suggested that LCFA (e.g. oleate) affected the expression of rpoS and exsC . DNA binding studies confirmed that PsrA binds to the rpoS and exsC promoter regions. This binding was inhibited by LCFA, indicating that LCFA directly affects the activation of these two genes through PsrA. LCFA decreased rpoS and exsC expression, resulting in increased N -(butyryl)- l -homoserine-lactone quorum sensing signal and decreased ExoS/T production respectively. Based on the crystal structure of PsrA, site-directed mutagenesis of amino acid residues, within the hydrophobic channel thought to accommodate LCFA, created two LCFA-non-responsive PsrA mutants. The binding and activation of rpoS and exsC by these PsrA mutants was no longer inhibited by LCFA. These data support a mechanistic model where LCFAs influence PsrA regulation to control LCFA metabolism and some virulence genes in P. aeruginosa . 相似文献
952.
Vladimir Elisashvili Eva Kachlishvili Nino Tsiklauri Eka Metreveli Tamar Khardziani Spiros N. Agathos 《World journal of microbiology & biotechnology》2009,25(2):331-339
The production of lignocellulolytic enzymes by eleven basidiomycetes species isolated from two ecosystems of Georgia was investigated
for the first time under submerged (SF) and solid-state fermentation (SSF) of lignocellulosic by-products. Notable intergeneric
and intrageneric differences were revealed with regard to the extent of hydrolase and oxidase activity. Several fungi produced
laccase along with hydrolases in parallel with growth during the trophophase, showing that the synthesis of this enzyme is
not connected with secondary metabolism. The lignocellulosic substrate type had the greatest impact on enzyme secretion. Some
of the substrates significantly stimulated lignocellulolytic enzyme synthesis without supplementation of the culture medium
with specific inducers. Exceptionally high carboxymethyl cellulase (CMCase, 122 U ml−1) and xylanase (195 U ml−1) activities were revealed in SF of mandarin peelings by Pseudotremella gibbosa IBB 22 and of residue after ethanol production (REP) by Fomes fomentarius IBB 38, respectively. The SSF of REP by T. pubescens IBB 11 ensured the highest level of laccase activity (24,690 U l−1), whereas the SSF of wheat bran and SF of mandarin peels provided the highest manganese peroxidase activity (570–620 U l−1) of Trichaptum biforme IBB 117. Moreover, the variation of lignocellulosic growth substrate provides an opportunity to obtain enzyme preparations
containing different ratios of individual enzymes. 相似文献
953.
Andrey E. Shchekotikhin Valeria A. Glazunova Lyubov G. Dezhenkova Yuri N. Luzikov Yuri B. Sinkevich Leonid V. Kovalenko Vladimir N. Buyanov Jan Balzarini Fong-Chun Huang Jing-Jer Lin Hsu-Shan Huang Alexander A. Shtil Maria N. Preobrazhenskaya 《Bioorganic & medicinal chemistry》2009,17(5):1861-1869
We developed the synthesis of a series of thiophene-fused tetracyclic analogues of the antitumor drug ametantrone. The reactions included nucleophilic substitution of methoxy groups in 4,11-dimethoxyanthra[2,3-b]thiophene-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione in good yields. Several compounds showed marked antiproliferative potency against doxorubicin-selected, P-glycoprotein-expressing tumor cells and p53?/? cells. The cytotoxicity of some novel compounds for P-glycoprotein-positive cells is highly dependent on N-substituent at the terminal amino group of ethylenediamine moiety. The cytotoxic potency of selected compounds correlated with their ability to attenuate the functions of topoisomerase I and telomerase, strongly suggesting that these enzymes are the major targets of antitumor activity of anthra[2,3-b]thiophene-5,10-dione derivatives. 相似文献
954.
955.
Vladimir G. Onipchenko Mikhail S. Blinnikov Maria A. Gerasimova Elena V. Volkova Johannes H.C. Cornelissen 《植被学杂志》2009,20(4):718-727
Question. Competitive and facilitative interactions among plant species in different abiotic environments potentially link productivity, vegetation structure, species composition and functional diversity. We investigated these interactions among four alpine communities along an environmental productivity gradient in a generally harsh climate. We hypothesised that the importance of competition would be higher in more productive sites. Location. Mt. M. Khatipara (43°27′N, 41°41′E, altitude 2750 m), NW Caucasus, Russia. Communities ranged from low‐productivity alpine lichen heath (ALH) and snowbed communities (SBC), to intermediate productivity Festuca grassland (FVG), and high‐productivity Geranium‐Hedysarum meadow (GHM). Methods. We quantified the relative influence of competition and facilitation on community structure by expressing biomass of target species within each natural community proportionally to biomass of the species in a “null community” with experimental release from interspecific competition by removing all other species (for 6 years). An overall index of change in community composition due to interspecific interactions was calculated as the sum of absolute or proportional differences of the component species. Results. Species responses to neighbour removal ranged from positive to neutral. There was no evidence of facilitation among the selected dominant species. As expected, competition was generally most important in the most productive alpine community (GHM). The intermediate position for low‐productivity communities of stressful environments (ALH, SBC) and the last position of intermediately productive FVG were unexpected. Conclusions. Our results appear to support the Fretwell‐Oksanen hypothesis in that competition in communities of intermediate productivity was less intense than in low‐ or high‐productive communities. However, the zero net effect of competition and facilitation in FVG might be the result of abiotic stress due to strong sun exposure and high soil temperatures after neighbour removal. Thus, non‐linear relationships between soil fertility, productivity and different abiotic stresses may also determine the balance between competition and facilitation. 相似文献
956.
957.
Mike Friedrich Revaz Nozadze Qiang Gan Vladimir Ermolayev Gregory S. Harms 《Biochemical and biophysical research communications》2009,390(3):722-8
Single-molecule detection and tracking is important for observing biomolecule interactions in the microenvironment. Here we report selective plane illumination microscopy (SPIM) with single-molecule detection in living organisms, which enables fast imaging and single-molecule tracking and optical penetration beyond 300 μm. We detected single nanocrystals in Drosophila larvae and zebrafish embryo. We also report our first tracking of single quantum dots during zebrafish development, which displays a transition from flow to confined motion prior to the blastula stage. The new SPIM setup represents a new technique, which enables fast single-molecule imaging and tracking in living systems. 相似文献
958.
Sarah Boissel Orit Reish Karine Proulx Hiroko Kawagoe-Takaki Giles S.H. Yeo Christelle Golzio Noman Kadhom Vladimir Saudek Philippe Froguel Tomas Lindahl Arnold Munnich 《American journal of human genetics》2009,85(1):106-310
FTO is a nuclear protein belonging to the AlkB-related non-haem iron- and 2-oxoglutarate-dependent dioxygenase family. Although polymorphisms within the first intron of the FTO gene have been associated with obesity, the physiological role of FTO remains unknown. Here we show that a R316Q mutation, inactivating FTO enzymatic activity, is responsible for an autosomal-recessive lethal syndrome. Cultured skin fibroblasts from affected subjects showed impaired proliferation and accelerated senescence. These findings indicate that FTO is essential for normal development of the central nervous and cardiovascular systems in human and establish that a mutation in a human member of the AlkB-related dioxygenase family results in a severe polymalformation syndrome. 相似文献
959.
Tatiana Petrova Vladimir Y. Lunin Isabelle Hazemann André Mitschler Andrzej Joachimiak 《Journal of molecular biology》2009,387(5):1092-825
X-rays interact with biological matter and cause damage. Proteins and other macromolecules are damaged primarily by ionizing X-ray photons and secondarily by reactive radiolytic chemical species. In particular, protein molecules are damaged during X-ray diffraction experiments with protein crystals, which is, in many cases, a serious hindrance to structure solution. The local X-ray-induced structural changes of the protein molecule have been studied using a number of model systems. However, it is still not well understood whether these local chemical changes lead to global structural changes in protein and what the mechanism is.We present experimental evidence at atomic resolution indicating the movement of large parts of the protein globule together with bound water molecules in the early stages of radiation damage to the protein crystal. The data were obtained from a crystal cryocooled to ~ 100 K and diffracting to 1 ?. The movement of the protein structural elements occurs simultaneously with the decarboxylation of several glutamate and aspartate residues that mediate contacts between moving protein structural elements and with the rearrangement of the water network. The analysis of the anisotropy of atomic displacement parameters reveals that the observed atomic movements occur at different rates in different unit cells of the crystal. Thus, the examination of the cooperative atomic movement enables us to better understand how radiation-induced local chemical and structural changes of the protein molecule eventually lead to disorder in protein crystals. 相似文献
960.
Hepatitis C virus NS5A protein modulates template selection by the RNA polymerase in in vitro system
Alexander V. Ivanov Vera L. Tunitskaya Vladimir A. Mitkevich Vladimir S. Prassolov Marina K. Kukhanova 《FEBS letters》2009,583(2):277-1996
Hepatitis C virus (HCV) NS5A phosphoprotein is a component of virus replicase. Here we demonstrate that in vitro unphosphorylated NS5A protein inhibits HCV RNA-dependent RNA polymerase (RdRp) activity in polyA-oligoU system but has little effect on synthesis of viral RNA. The phosphorylated casein kinase (CK) II NS5A protein causes the opposite effect on RdRp in each of these systems. The phosphorylation of NS5A protein with CKII does not affect its affinity to the HCV RdRp and RNA. The NS5A phosphorylation with CKI does not change the RdRp activity. Herein we report evidence that the NS5A prevents template binding to the RdRp.