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排序方式: 共有997条查询结果,搜索用时 15 毫秒
861.
Kenji Yoshikawa Aki Yokomizo Hiroyuki Naito Noriyasu Haginoya Shozo Kobayashi Toshiharu Yoshino Tsutomu Nagata Akiyoshi Mochizuki Ken Osanai Kengo Watanabe Hideyuki Kanno Toshiharu Ohta 《Bioorganic & medicinal chemistry》2009,17(24):8206-8220
A series of cis-1,2-diaminocyclohexane derivatives were synthesized with the aim of optimizing previously disclosed factor Xa (fXa) inhibitors. The exploration of 5–6 fused rings as alternative S1 moieties resulted in two compounds which demonstrated improved solubility and reduced food effect compared to the clinical candidate, compound A. Herein, we describe the synthesis and structure–activity relationship (SAR), together with the physicochemical properties and pharmacokinetic (PK) profiles of some prospective compounds. 相似文献
862.
Rapid, sensitive and simple detection method for koi herpesvirus using loop-mediated isothermal amplification 总被引:1,自引:0,他引:1
Manabu Yoshino Hajime Watari Tadashi Kojima Masanari Ikedo Jun Kurita 《Microbiology and immunology》2009,53(7):375-383
New methods were developed for the detection of koi herpesvirus (KHV, CyHV-3) by LAMP, which were compared with the PCR for specificity and sensitivity. We designed two primer sets targeting a specific sequence within the 9/5 PCR amplicon (9/5 LAMP) and the upper region of the Sph I-5 PCR amplicon ( Sph I-5 LAMP), including a sequence highly conserved among the strains. The amplification was monitored in real-time based on the increase in turbidity, with magnesium pyrophosphate as the by-product. The reactions were carried out under isothermal conditions at 65°C for 60 min. The detection limit of both LAMP was six copies, equal to the modified Sph I-5 PCR. No cross-reactivity with other fish pathogenic viruses and bacteria was observed. Sph I-5 LAMP was found to have a quicker response in terms of the reaction velocity than 9/5 LAMP. Therefore, we consider Sph I-5 LAMP to be superior for routine use. Additionally, LAMP was found applicable to crude extract from gills and other organs. LAMP methods are superior in terms of sensitivity, specificity, rapidity and simplicity, and are potentially a valuable diagnostic tool for KHV infections. 相似文献
863.
Yoshino Ando Shunsuke Utsumi Takayuki Ohgushi 《Entomologia Experimentalis et Applicata》2010,136(2):174-183
We compared community composition, density, and species richness of herbivorous insects on the introduced plant Solidago altissima L. (Asteraceae) and the related native species Solidago virgaurea L. in Japan. We found large differences in community composition on the two Solidago species. Five hemipteran sap feeders were found only on S. altissima. Two of them, the aphid Uroleucon nigrotuberculatum Olive (Hemiptera: Aphididae) and the scale insect Parasaissetia nigra Nietner (Hemiptera: Coccidae), were exotic species, accounting for 62% of the total individuals on S. altissima. These exotic sap feeders mostly determined the difference of community composition on the two plant species. In contrast, the herbivore community on S. virgaurea consisted predominately of five native insects: two lepidopteran leaf chewers and three dipteran leaf miners. Overall species richness did not differ between the plants because the increased species richness of sap feeders was offset by the decreased richness of leaf chewers and leaf miners on S. altissima. The overall density of herbivorous insects was higher on S. altissima than on S. virgaurea, because of the high density of the two exotic sap feeding species on S. altissima. We discuss the importance of analyzing community composition in terms of feeding guilds of insect herbivores for understanding how communities of insect herbivores are organized on introduced plants in novel habitats. 相似文献
864.
T. VEHANEN A. HUUSKO A. MÄKI‐PETÄYS P. LOUHI H. MYKRÄ T. MUOTKA 《Freshwater Biology》2010,55(10):2200-2214
1. Degradation of stream habitat because of anthropogenic activities (e.g. channelisation) has had a dramatic impact on fluvial environments and their biota, and as a consequence, increasing effort has been directed towards the restoration of degraded rivers. However, a major problem is that the success (or failure) of restoration has been rarely tested using a well‐designed monitoring programme to allow reliable detection of an impact, if any exists. We used a spatially and temporally replicated, balanced Before‐After‐Control‐Impact design to assess the impact of stream habitat rehabilitation on the densities and growth of brown trout of three age‐classes in North Finnish forest streams. 2. Three separate sections in each of six streams were selected for the study. After 3 years of pre‐rehabilitation monitoring, two randomly selected sections in each stream were restored; one using large woody debris and boulders and the other using only boulders. A third section remained as an unmodified control. Monitoring of fish densities continued for 3 years after rehabilitation. 3. Rehabilitation clearly increased streambed complexity, but did not have detectable effects on brown trout stocks in either of the rehabilitation schemes (LWD or stones), except for age‐2+ and older fish which decreased in abundance compared to control reaches. A severe drought after rehabilitation in late summer 2002 reduced densities of trout to a low level in all streams, overriding any local effects of rehabilitation. Rehabilitation structures seemed to provide some safeguard against drought for age‐2 and older, but not for the younger age‐classes. 4. Our results add to the growing body of literature suggesting that large‐scale regional factors may overwhelm local management efforts. To be successful in the future, stream rehabilitation schemes must include drought refuge areas for fish and other stream biota. 相似文献
865.
866.
Lee MC Kawai Y Shoji H Yoshino F Miyazaki H Kato H Suga M Kubota E 《Redox report : communications in free radical research》2004,9(6):331-336
Reactive oxygen species (ROS) have been implicated in the pathogenesis of temporomandibular disorders. In the present study, we provide the first evidence of ROS generation in the synovial fluid from human temporomandibular disorder patients, as shown by electron spin resonance (ESR) and spin trapping. Three distinct ESR spectra of DMPO spin adducts were observed in the synovial fluid. They corresponded to three free radical species: hydroxyl radical (HO(*)), hydrogen radical (H(*)), and carbon-center radical (R(*)). Among them, the 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)-OH spectrum was the most prominent, suggesting that HO(*) was dominantly generated in the synovial fluid from temporomandibular disorder patients. Desferrioxamine (DFO), an iron chelator, strongly depressed the DMPO-OH signal intensity in the synovial fluid from patients with temporomandibular disorders. We successfully demonstrated ROS-induced oxidative stress in the synovial fluid from temporomandibular disorder patients. ROS generation in the temporomandibular joint could lead to exacerbation of inflammation and activation of cartilage matrix degrading enzymes that proceed to degenerative change of the temporomandibular joint. Thus, iron-dependent generation of HO( *) might have a crucial role in the pathogenesis of temporomandibular disorders. 相似文献
867.
868.
Vadakkanchery V Vaidyanathan Ken-ichi Yoshino Michael Jahnz Christos Dörries Steffen Bade Sonja Nauenburg Heiner Niemann & Thomas Binz 《Journal of neurochemistry》1999,72(1):327-337
Abstract : Tetanus toxin and the seven serologically distinct botulinal neurotoxins (BoNT/A to BoNT/G) abrogate synaptic transmission at nerve endings through the action of their light chains (L chains), which proteolytically cleave VAMP (vesicle-associated membrane protein)/synaptobrevin, SNAP-25 (synaptosome-associated protein of 25 kDa), or syntaxin. BoNT/C was reported to proteolyze both syntaxin and SNAP-25. Here, we demonstrate that cleavage of SNAP-25 occurs between Arg198 and Ala199 , depends on the presence of regions Asn93 to Glu145 and Ile156 to Met202 , and requires about 1,000-fold higher L chain concentrations in comparison with BoNT/A and BoNT/E. Analyses of the BoNT/A and BoNT/E cleavage sites revealed that changes in the carboxyl-terminal residues, in contrast with changes in the amino-terminal residues, drastically impair proteolysis. A proteolytically inactive BoNT/A L chain mutant failed to bind to VAMP/synaptobrevin and syntaxin, but formed a stable complex ( K D = 1.9 × 10-7 M ) with SNAP-25. The minimal essential domain of SNAP-25 required for cleavage by BoNT/A involves the segment Met146 -Gln197 , and binding was optimal only with full-length SNAP-25. Proteolysis by BoNT/E required the presence of the domain Ile156 -Asp186 . Murine SNAP-23 was cleaved by BoNT/E and, to a reduced extent, by BoNT/A, whereas human SNAP-23 was resistant to all clostridial L chains. Lys185 Asp or Pro182 Arg mutations of human SNAP-23 induced susceptibility toward BoNT/E or toward both BoNT/A and BoNT/E, respectively. 相似文献
869.
W. I. J. DIELEMAN S. LUYSSAERT A. REY P. DE ANGELIS C. V. M. BARTON M. S. J. BROADMEADOW S. B. BROADMEADOW K. S. CHIGWEREWE M. CROOKSHANKS E. DUFRÊNE P. G. JARVIS A. KASURINEN S. KELLOMÄKI V. LE DANTEC M. LIBERLOO M. MAREK B. MEDLYN R. POKORNÝ G. SCARASCIA‐MUGNOZZA V. M. TEMPERTON D. TINGEY O. URBAN R. CEULEMANS I. A. JANSSENS 《Plant, cell & environment》2010,33(12):2001-2011
Under elevated atmospheric CO2 concentrations, soil carbon (C) inputs are typically enhanced, suggesting larger soil C sequestration potential. However, soil C losses also increase and progressive nitrogen (N) limitation to plant growth may reduce the CO2 effect on soil C inputs with time. We compiled a data set from 131 manipulation experiments, and used meta‐analysis to test the hypotheses that: (1) elevated atmospheric CO2 stimulates soil C inputs more than C losses, resulting in increasing soil C stocks; and (2) that these responses are modulated by N. Our results confirm that elevated CO2 induces a C allocation shift towards below‐ground biomass compartments. However, the increased soil C inputs were offset by increased heterotrophic respiration (Rh), such that soil C content was not affected by elevated CO2. Soil N concentration strongly interacted with CO2 fumigation: the effect of elevated CO2 on fine root biomass and –production and on microbial activity increased with increasing soil N concentration, while the effect on soil C content decreased with increasing soil N concentration. These results suggest that both plant growth and microbial activity responses to elevated CO2 are modulated by N availability, and that it is essential to account for soil N concentration in C cycling analyses. 相似文献
870.
Yoshino N Ami Y Someya K Ando S Shinohara K Tashiro F Lu Y Honda M 《Microbiology and immunology》2000,44(5):363-372
A simian/human immunodeficiency virus (SHIV)-NM3n containing the human nef, but not the monkey nef, and vpr genes of SIV was inoculated into two cynomolgus monkeys, resulting in systemic infection with a minimum level of transient virus load. In order to study the nature of immune responses associated with the prevention of a pathogenic SHIV, the SHIV-NM3n-inoculated monkeys and three naive monkeys were intravenously challenged with a pathogenic SHIV containing the envelope gene of HIV-1 89.6. After the heterologous virus challenge, all of the SHIV-NM3n-inoculated animals completely avoided the loss of CD4+ T lymphocytes in PBMC as well as lymphoid tissues compared to pathogenic SHIV-injected control animals. The inhibition of CD4+ cell depletion was associated with maintaining the proliferative response of helper T-cells against SIV p27 in the previously nonpathogenic virus-inoculated animals following the pathogenic virus challenge. Furthermore, the decline of CD28+ cells, the increase in CD95+ cells, and the enhancement of in vitro apoptosis in PBMC were inhibited in the non-pathogenic virus-inoculated animals. These results suggest that nonpathogenic SHIV-NM3n infection induces the protection of monkeys from heterologous pathogenic viruses that may be associated with blocking the change in immune responses and the cell loss induced by a pathogenic virus. 相似文献