全文获取类型
收费全文 | 3132篇 |
免费 | 160篇 |
国内免费 | 3篇 |
专业分类
3295篇 |
出版年
2022年 | 14篇 |
2021年 | 20篇 |
2020年 | 16篇 |
2019年 | 19篇 |
2018年 | 40篇 |
2017年 | 31篇 |
2016年 | 45篇 |
2015年 | 67篇 |
2014年 | 89篇 |
2013年 | 240篇 |
2012年 | 147篇 |
2011年 | 178篇 |
2010年 | 103篇 |
2009年 | 111篇 |
2008年 | 178篇 |
2007年 | 193篇 |
2006年 | 215篇 |
2005年 | 206篇 |
2004年 | 200篇 |
2003年 | 198篇 |
2002年 | 196篇 |
2001年 | 29篇 |
2000年 | 32篇 |
1999年 | 35篇 |
1998年 | 33篇 |
1997年 | 43篇 |
1996年 | 39篇 |
1995年 | 50篇 |
1994年 | 33篇 |
1993年 | 44篇 |
1992年 | 41篇 |
1991年 | 21篇 |
1990年 | 25篇 |
1989年 | 20篇 |
1988年 | 25篇 |
1987年 | 19篇 |
1986年 | 12篇 |
1985年 | 28篇 |
1984年 | 21篇 |
1983年 | 29篇 |
1982年 | 30篇 |
1981年 | 29篇 |
1980年 | 26篇 |
1979年 | 10篇 |
1978年 | 20篇 |
1977年 | 15篇 |
1976年 | 12篇 |
1975年 | 9篇 |
1974年 | 11篇 |
1973年 | 13篇 |
排序方式: 共有3295条查询结果,搜索用时 15 毫秒
101.
We have examined whether ciliary neurotrophic factor (CNTF) can alter serum-free cell survival of immortalized motor neuron-like cells, which were established by fusing mouse neuroblasoma N18TG2 with mouse motor neurons. One of the cell lines, NSC-34 exhibited cell survival in the presence of CNTF. NSC-34 preserves the most characteristics of motor neurons, such as the formation of neuromuscular junctions on co-cultured myotube. GM2 ganglioside is characteristic of motor neurons, and expressed highly in NSC-34. When NSC-34 was cultured with exogenous GM2 ganglioside and CNTF, GM2 facilitated the cell survival effect of CNTF. In the addition, 1,4 N-acetylgalactosaminyltransferase (GM2 synthase) activity was enhanced up to 3.9-fold by culture in the presence of CNTF. GM2 might be a functional modulator of CNTF in motor neurons. It might be presented to cell surface by its enzyme activation, and become a signal of early stage, when CNTF rescues motor neurons. 相似文献
102.
Severe reduction in growth rate and grain filling of rice mutants lacking OsGS1;1, a cytosolic glutamine synthetase1;1 总被引:10,自引:0,他引:10
Tabuchi M Sugiyama K Ishiyama K Inoue E Sato T Takahashi H Yamaya T 《The Plant journal : for cell and molecular biology》2005,42(5):641-651
Rice (Oryza sativa L.) plants possess three homologous but distinct genes for cytosolic glutamine synthetase (GS1): these are OsGS1;1, OsGS1;2, and OsGS1;3. OsGS1;1 was expressed in all organs tested with higher expression in leaf blades, while OsGS1;2, and OsGS1;3 were expressed mainly in roots and spikelets, respectively. We characterized knockout mutants caused by insertion of endogenous retrotransposon Tos17 into the exon-8 (lines ND8037 and ND9801) or the exon-10 (line NC2327) of OsGS1;1. Mendelian segregation occurred in each progeny. Homozygously inserted mutants showed severe retardation in growth rate and grain filling when grown at normal nitrogen concentrations. Abnormal mRNA for GS1;1 was transcribed, and the GS1 protein and its activity in the leaf blades were barely detectable in these mutants. The glutamine pool in the roots and leaf blades of the mutants was lower than that of the wild type. Re-introduction of OsGS1;1 cDNA under the control of its own promoter into the mutants successfully complemented these phenotypes. Progeny where Tos17 was heterozygously inserted or deleted during segregation showed normal phenotypes. The results indicate that GS1;1 is important for normal growth and grain filling in rice; GS1;2 and GS1;3 were not able to compensate for GS1;1 function. 相似文献
103.
Tadashi Fukami T. Martijn Bezemer Simon R. Mortimer Wim H. van der Putten 《Ecology letters》2005,8(12):1283-1290
Despite decades of research, it remains controversial whether ecological communities converge towards a common structure determined by environmental conditions irrespective of assembly history. Here, we show experimentally that the answer depends on the level of community organization considered. In a 9‐year grassland experiment, we manipulated initial plant composition on abandoned arable land and subsequently allowed natural colonization. Initial compositional variation caused plant communities to remain divergent in species identities, even though these same communities converged strongly in species traits. This contrast between species divergence and trait convergence could not be explained by dispersal limitation or community neutrality alone. Our results show that the simultaneous operation of trait‐based assembly rules and species‐level priority effects drives community assembly, making it both deterministic and historically contingent, but at different levels of community organization. 相似文献
104.
Yoshiji H Noguchi R Kuriyama S Ikenaka Y Yoshii J Yanase K Namisaki T Kitade M Masaki T Fukui H 《American journal of physiology. Gastrointestinal and liver physiology》2005,288(5):G907-G913
It is widely recognized that activated hepatic stellate cells (HSC) play a pivotal role in development of liver fibrosis. A platelet-derived growth factor (PDGF) is the most potent mitogen for HSC. The aim of this study was to examine the effect of imatinib mesylate (STI-571, Gleevec), a clinically used PDGF receptor (PDGFR) tyrosine kinase inhibitor, on development of experimental liver fibrosis. The rat model of pig serum-induced hepatic fibrosis was used to assess the effect of daily oral administration of STI-571 on the indexes of fibrosis. STI-571 markedly attenuated development of liver fibrosis and hepatic hydroxyproline and serum fibrosis markers. The number of alpha-smooth muscle actin-positive cells and mRNA expression of alpha2-(I)-procollagen, tissue inhibitor of metalloproteinases-1, and transforming growth factor-beta were also significantly suppressed by STI-571. Our in vitro study showed that STI-571 markedly attenuated PDGF-BB-induced proliferation and migration and alpha-SMA and alpha2-(I)-procollagen mRNA of activated HSC in a dose-dependent manner. STI-571 also significantly attenuated PDGF-BB-induced phosphorylation of PDGFR-beta, MEK1/2, and Akt in activated HSC. Because STI-571 is widely used in clinical practice, it may provide an effective new strategy for antifibrosis therapy. 相似文献
105.
Nishiya T Matsumoto K Maekawa S Kajita E Horinouchi T Fujimuro M Ogasawara K Uehara T Miwa S 《The Journal of biological chemistry》2011,286(11):9009-9019
Inducible nitric-oxide synthase (iNOS, NOS2) plays a prominent role in macrophage bactericidal and tumoricidal activities. A relatively large amount of NO produced via iNOS, however, also targets the macrophage itself for apoptotic cell death. To uncover the intrinsic mechanisms of iNOS regulation, we have characterized the SPRY domain- and SOCS box-containing protein 1 (SPSB1), SPSB2, and SPSB4 that interact with the N-terminal region of iNOS in a D-I-N-N-N sequence-dependent manner. Fluorescence microscopy revealed that these SPSB proteins can induce the subcellular redistribution of iNOS from dense regions to diffused expression in a SOCS box-dependent manner. In immunoprecipitation studies, both Elongin C and Cullin-5, components of the multi-subunit E3 ubiquitin ligase, were found to bind to iNOS via SPSB1, SPSB2, or SPSB4. Consistently, iNOS was polyubiquitinated and degraded in a proteasome-dependent manner when SPSB1, SPSB2, or SPSB4 was expressed. SPSB1 and SPSB4 had a greater effect on iNOS regulation than SPSB2. The iNOS N-terminal fragment (residues 1-124 of human iNOS) could disrupt iNOS-SPSB interactions and inhibit iNOS degradation. In lipopolysaccharide-treated macrophages, this fragment attenuated iNOS ubiquitination and substantially prolonged iNOS lifetime, resulting in a corresponding increase in NO production and enhanced NO-dependent cell death. These results not only demonstrate the mechanism of SPSB-mediated iNOS degradation and the relative contributions of different SPSB proteins to iNOS regulation, but also show that iNOS levels are sophisticatedly regulated by SPSB proteins in activated macrophages to prevent overproduction of NO that could trigger detrimental effects, such as cytotoxicity. 相似文献
106.
It has been increasingly recognized that landscape matrices are an important factor determining patch connectivity and hence the population size of organisms living in highly fragmented landscapes. However, most previous studies estimated the effect of matrix heterogeneity using prior information regarding dispersal or habitat preferences of a focal organism. Here we estimated matrix resistance of harvest mice in agricultural landscapes using a novel pattern‐oriented modeling with Bayesian estimation and no prior information, and then conducted model validation using data sets independent from those used for model construction. First, we investigated the distribution patterns of harvest mice for approximately 400 habitat patches, and estimated matrix resistance for different matrix types using statistical models incorporating patch size, patch environment, and patch connectivity. We used Bayesian estimation with a Markov chain Monte Carlo algorithm, and searched for appropriate matrix resistance that best explained the distribution pattern. Patch connectivity as well as patch quality was an important determinant of local population size for the harvest mice. Moreover, matrix resistance was far from uniform, with rice and crop fields exhibiting low resistance and forests, creeks, roads and residential areas showing much higher resistance. The deviance explained by this model (heterogeneous matrix model) was much larger than that obtained by the model with no consideration of matrix heterogeneity (homogeneous matrix model). Second, we obtained distribution data from five additional landscapes that were more fragmented than that used for model construction, and used them for model validation. The heterogeneous matrix model well predicted the population size for four out of five landscapes. In contrast, the homogeneous model considerably overestimated population sizes in all cases. Our approach is widely applicable to species living in fragmented landscapes, especially those for which prior information regarding movement or dispersal is difficult to obtain. 相似文献
107.
Chang YC Ikeutsu K Toyama T Choi D Kikuchi S 《Journal of industrial microbiology & biotechnology》2011,38(10):1667-1677
Two rapidly growing propionibacteria that could reductively dechlorinate tetrachloroethylene (PCE) and cis-1,2-dichloroethylene (cis-DCE) to ethylene were isolated from environmental sediments. Metabolic characterization and partial sequence analysis of
their 16S rRNA genes showed that the new isolates, designated as strains Propionibacterium sp. HK-1 and Propionibacterium sp. HK-3, did not match any known PCE- or cis-DCE-degrading bacteria. Both strains dechlorinated relatively high concentrations of PCE (0.3 mM) and cis-DCE (0.52 mM) under anaerobic conditions without accumulating toxic intermediates during incubation. Cell-free extracts of
both strains catalyzed PCE and cis-DCE dechlorination; degradation was accelerated by the addition of various electron donors. PCE dehalogenase from strain
HK-1 was mediated by a corrinoid protein, since the dehalogenase was inactivated by propyl iodide only after reduction by
titanium citrate. The amounts of chloride ions (0.094 and 0.103 mM) released after PCE (0.026 mM) and cis-DCE (0.05 mM) dehalogenation using the cell-free enzyme extracts of both strains, HK-1 and HK-3, were stoichiometrically
similar (91 and 100%), indicating that PCE and cis-DCE were fully dechlorinated. Radiotracer studies with [1,2-14C] PCE and [1,2-14C] cis-DCE indicated that ethylene was the terminal product; partial conversion to ethylene was observed. Various chlorinated aliphatic
compounds (PCE, trichloroethylene, cis-DCE, trans-1,2-dichloroethylene, 1,1-dichloroethylene, 1,1-dichloroethane, 1,2-dichloroethane, 1,2-dichloropropane, 1,1,2-trichloroethane,
and vinyl chloride) were degraded by cell-free extracts of strain HK-1. 相似文献
108.
Objective
Nasal obstruction is a common problem in continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea and limits treatment compliance. The purpose of this study is to model the effects of nasal obstruction on airflow parameters under CPAP using computational fluid dynamics (CFD), and to clarify quantitatively the relation between airflow velocity and pressure loss coefficient in subjects with and without nasal obstruction.Methods
We conducted an observational cross-sectional study of 16 Japanese adult subjects, of whom 9 had nasal obstruction and 7 did not (control group). Three-dimensional reconstructed models of the nasal cavity and nasopharynx with a CPAP mask fitted to the nostrils were created from each subject’s CT scans. The digital models were meshed with tetrahedral cells and stereolithography formats were created. CPAP airflow simulations were conducted using CFD software. Airflow streamlines and velocity contours in the nasal cavities and nasopharynx were compared between groups. Simulation models were confirmed to agree with actual measurements of nasal flow rate and with pressure and flow rate in the CPAP machine.Results
Under 10 cmH2O CPAP, average maximum airflow velocity during inspiration was 17.6 ± 5.6 m/s in the nasal obstruction group but only 11.8 ± 1.4 m/s in the control group. The average pressure drop in the nasopharynx relative to inlet static pressure was 2.44 ± 1.41 cmH2O in the nasal obstruction group but only 1.17 ± 0.29 cmH2O in the control group. The nasal obstruction and control groups were clearly separated by a velocity threshold of 13.5 m/s, and pressure loss coefficient threshold of approximately 10.0. In contrast, there was no significant difference in expiratory pressure in the nasopharynx between the groups.Conclusion
This is the first CFD analysis of the effect of nasal obstruction on CPAP treatment. A strong correlation between the inspiratory pressure loss coefficient and maximum airflow velocity was found. 相似文献109.
110.
Sueyoshi Kuni; Kubo Yoshihiro; Yamagishi Kenji; Ogura Nagao; Ochiai Kuniyasu; Fukushima Kazuo; Ikeda Tadashi; Nakagawa Hiroki 《Plant & cell physiology》1988,29(6):975-980
Two monoclonal antibodies, 17(3)9 and 36(79)4, were preparedagainst nitrate reductase from Spinacia oleracea L. leaves.An enzyme-linked immunosorbent assay showed that 17(3)9, butnot 36(79)4, reacted more strongly to heat-denatured than nativeantigen. These antibodies inhibited NADH-nitrate reductase aswell as its various partial activities including reduced methylvilogen-nitrate reductase, reduced flavin mononucleotide-nitratereductase and NADH-cytochrome c reductase activities, but notNADH-ferricyanide reductase activity. Immunoblotting after electrophoreticseparation of nitrate reductase fragments obtained by Staphyrococcusaureus V8 protease digestion of native enzyme revealed thatthe two monoclonal antibodies bind to different epitopes locatedon the 28 kDa of the NADH-ferricyanide reductase domain. (Received October 2, 1987; Accepted June 9, 1988) 相似文献