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81.
Interleukin-1α (IL-1α) is a proinflammatory cytokine and a key player in host immune responses in higher eukaryotes. IL-1α has pleiotropic effects on a wide range of cell types, and it has been extensively studied for its ability to contribute to various autoimmune and inflammation-linked disorders, including rheumatoid arthritis, Alzheimer's disease, systemic sclerosis and cardiovascular disorders. Interestingly, a significant proportion of IL-1α is translocated to the cell nucleus, in which it interacts with histone acetyltransferase complexes. Despite the importance of IL-1α, little is known regarding its binding targets and functions in the nucleus. We took advantage of the histone acetyltransferase (HAT) complexes being evolutionarily conserved from yeast to humans and the yeast SAGA complex serving as an epitome of the eukaryotic HAT complexes. Using gene knock-out technique and co-immunoprecipitation of the IL-1α precursor with TAP-tagged subunits of the yeast HAT complexes, we mapped the IL-1α-binding site to the HAT/Core module of the SAGA complex. We also predicted the 3-D structure of the IL-1α N-terminal domain, and by employing structure similarity searches, we found a similar structure in the C-terminal regulatory region of the catalytic subunit of the AMP-activated/Snf1 protein kinases, which interact with HAT complexes both in mammals and yeast, respectively. This finding is further supported with the ability of the IL-1α precursor to partially rescue growth defects of snf1Δ yeast strains on media containing 3-Amino-1,2,4-triazole (3-AT), a competitive inhibitor of His3. Finally, the careful evaluation of our data together with other published data in the field allows us to hypothesize a new function for the ADA complex in SAGA complex assembly. 相似文献
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83.
Martin Straka Ladislav Paule Ovidiu Ionescu Jozef ?tofík Michal Adamec 《Conservation Genetics》2012,13(1):153-164
The formerly large, continuous brown bear population of the Carpathians has experienced a radical decrease in population size
due to human activities which have resulted in splitting the population into the larger Eastern Carpathian and the smaller
Western Carpathian subpopulations. In the Western Carpathians, brown bears came close to extinction at the beginning of 1930s,
but thanks to both conservation and management efforts the bear population has begun to recover. In contrast, the Eastern
Carpathian subpopulation in Romania has never dropped below 800 individuals, potentially preserving the original amount of
genetic variation. In this paper we present results of a genetic study of brown bear subpopulations distributed in the Slovak
and Romanian sections of the Carpathians using 13 nuclear microsatellites. The documented level of genetic differentiation
between the Western and Eastern Carpathian subpopulations reflects the isolation which lasted almost 100 years. Furthermore,
the existence of two, different, genetic clusters within the Western Carpathians despite close geographic proximity indicates
that human-caused fragmentation and isolation have resulted in significant genetic divergence. Although the subpopulations
display an indication of genetic bottleneck, the level of genetic diversity is within the range commonly observed in different
brown bear populations. The results presented here point out the significance of human exploitation to the population structure
of this large carnivore species. Future management efforts should be aimed at securing and restoring the connectivity of forested
habitats, in order to preserve the genetic variation of the Carpathian brown bear subpopulations and to support the gene flow
between them. 相似文献
84.
Genetic diversity, structure, and size of an endangered brown bear population threatened by highway construction in the Pindos Mountains, Greece 总被引:1,自引:0,他引:1
Alexandros A. Karamanlidis Martin Straka Elena Drosopoulou Miguel de Gabriel Hernando Ivna Kocijan Ladislav Paule Zacharias Scouras 《European Journal of Wildlife Research》2012,58(3):511-522
One of the major negative effects of roads is the creation of barriers to the movement of wildlife, ultimately disconnecting populations and increasing extinction risk. We collected genetic data from a threatened brown bear population in the central part of the Pindos mountain range in northwestern Greece to provide information about this, as yet genetically undescribed, population and to evaluate its status prior to the construction of a major highway. We used noninvasive genetic sampling methods and microsatellite analysis to investigate nuclear genetic diversity, population genetic structure, demographic history, relatedness within the population and estimated effective and total population size. Brown bears in the study area were found to possess a relatively high level of nuclear genetic diversity and low levels of inbreeding; the population did not show any signs of substructuring but seems to have gone through a genetic bottleneck in the recent past. The estimated effective population size was 29, and the total population size estimate obtained by two different methods was 33 and 51 individuals, respectively. Our results indicate a good conservation status of this bear population and provide baseline genetic data for the future evaluation of the effects on bears from the construction of a major highway, for monitoring the genetic status of this and other bear populations in Greece and for assessing gene flow in bear populations in southern Europe. 相似文献
85.
Radovan Fiser Jiri Masin Ladislav Bumba Eva Pospisilova Catherine Fayolle Marek Basler Lenka Sadilkova Irena Adkins Jana Kamanova Jan Cerny Ivo Konopasek Radim Osicka Claude Leclerc Peter Sebo 《PLoS pathogens》2012,8(4)
Bordetella adenylate cyclase toxin-hemolysin (CyaA) penetrates the cytoplasmic membrane of phagocytes and employs two distinct conformers to exert its multiple activities. One conformer forms cation-selective pores that permeabilize phagocyte membrane for efflux of cytosolic potassium. The other conformer conducts extracellular calcium ions across cytoplasmic membrane of cells, relocates into lipid rafts, translocates the adenylate cyclase enzyme (AC) domain into cells and converts cytosolic ATP to cAMP. We show that the calcium-conducting activity of CyaA controls the path and kinetics of endocytic removal of toxin pores from phagocyte membrane. The enzymatically inactive but calcium-conducting CyaA-AC− toxoid was endocytosed via a clathrin-dependent pathway. In contrast, a doubly mutated (E570K+E581P) toxoid, unable to conduct Ca2+ into cells, was rapidly internalized by membrane macropinocytosis, unless rescued by Ca2+ influx promoted in trans by ionomycin or intact toxoid. Moreover, a fully pore-forming CyaA-ΔAC hemolysin failed to permeabilize phagocytes, unless endocytic removal of its pores from cell membrane was decelerated through Ca2+ influx promoted by molecules locked in a Ca2+-conducting conformation by the 3D1 antibody. Inhibition of endocytosis also enabled the native B. pertussis-produced CyaA to induce lysis of J774A.1 macrophages at concentrations starting from 100 ng/ml. Hence, by mediating calcium influx into cells, the translocating conformer of CyaA controls the removal of bystander toxin pores from phagocyte membrane. This triggers a positive feedback loop of exacerbated cell permeabilization, where the efflux of cellular potassium yields further decreased toxin pore removal from cell membrane and this further enhances cell permeabilization and potassium efflux. 相似文献
86.
87.
Andrej A. Romanovsky Alexandre A. Steiner Luiz G. S. Branco Ladislav Janský Valery N. Gourine 《Journal of thermal biology》2004,29(7-8):407-411
(1) Administration of arginine vasopressin (AVP) in the ventral septal area (VSA) or intracerebroventricularly (i.c.v.) is thought to attenuate lipopolysaccharide (LPS) or prostaglandin (PG) E2 fevers in rabbits and rats by acting on the V1 receptor. (2) We found that the fever response of rabbits to intravenous LPS (200 ng/kg) or intra-VSA PGE2 (500 ng) was not attenuated but enhanced by intra-VSA AVP (5 μg); a pharmacological analysis showed that this fever-enhancing effect was mediated by the V2 receptor. (3) The febrile response of rats to intraperitoneal (50 μg/kg) or i.c.v. (100 ng) LPS was unaffected by i.c.v. AVP (2.5–100 ng). (4) The role of AVP in fever should be re-examined. 相似文献
88.
Abstract. The clonal sedge Carex humilis forms rings of densely aggregated ramets in a dry grassland community in Central Europe. We describe the small‐scale spatial variation, both in abiotic factors and vegetation, in relation to these rings. Compared to the surrounding vegetation the cover of plants, other than C. humilis, was significantly lower both in the central area of rings and within the rings themselves. The vegetation structure was also different. The soil was more fertile in the central area and within the ring than in the surroundings, measured both directly and by the abiotic response values of the vascular plants. We conclude that neither resource depletion nor competition from other plants were likely to be responsible for the low ramet density in the central area of C. humilis rings. Instead, we suggest that the ring form is caused either by the deposition of growth inhibiting substances or by intrinsic morphological rules. 相似文献
89.
90.