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Frank Lennartz Karen Bayer Nadine Czerwonka Yinghui Lu Kristine Kehr Manuela Hirz Torsten Steinmetzer Wolfgang Garten Christiane Herden 《Cellular microbiology》2016,18(3):340-354
Borna disease virus (BDV) is a non‐segmented negative‐stranded RNA virus that maintains a strictly neurotropic and persistent infection in affected end hosts. The primary target cells for BDV infection are brain cells, e.g. neurons and astrocytes. The exact mechanism of how infection is propagated between these cells and especially the role of the viral glycoprotein (GP) for cell–cell transmission, however, are still incompletely understood. Here, we use different cell culture systems, including rat primary astrocytes and mixed cultures of rat brain cells, to show that BDV primarily spreads through cell–cell contacts. We employ a highly stable and efficient peptidomimetic inhibitor to inhibit the furin‐mediated processing of GP and demonstrate that cleaved and fusion‐active GP is strictly necessary for the cell‐to‐cell spread of BDV. Together, our quantitative observations clarify the role of Borna disease virus‐glycoprotein for viral dissemination and highlight the regulation of GP expression as a potential mechanism to limit viral spread and maintain persistence. These findings furthermore indicate that targeting host cell proteases might be a promising approach to inhibit viral GP activation and spread of infection. 相似文献
84.
Molecular phylogeny of Harpactorinae and Bactrodinae uncovers complex evolution of sticky trap predation in assassin bugs (Heteroptera: Reduviidae) 下载免费PDF全文
Junxia Zhang Christiane Weirauch Guanyang Zhang Dimitri Forero 《Cladistics : the international journal of the Willi Hennig Society》2016,32(5):538-554
Sticky trap predation, the use of adhesive substances to trap and capture prey, is an intriguing yet poorly studied predatory strategy. Unique among known sticky trap predators, assassin bugs (Reduviidae) have evolved both exogenous and endogenous sticky trap predatory mechanisms: some trap their prey with sticky plant resins, some scavenge insects entrapped by sticky plant trichomes and others self‐produce sticky secretions. The evolution of these different strategies in assassin bugs is poorly understood due to the lack of comprehensive phylogenies. We reconstruct a phylogeny of Reduviidae (141 taxa; > 5000 bp) focusing on the Harpactorinae and Bactrodinae that engage in sticky trap predation. Ancestral state reconstruction, and temporal and geographical divergence analyses show that sticky trap predation techniques in assassin bugs evolved at least seven times independently since the late Cretaceous: use of sticky plant trichomes evolved as many as four times, resin‐use twice independently and once as a transition from trichome use, and ‘self‐stickiness’ once. Exogenous and endogenous sticky traps first appeared in the Neotropics, with the two exogenous mechanisms (resin and trichome use) subsequently evolving independently in the Old World. This study illustrates, for the first time, the complex evolutionary pattern of sticky trap predation within assassin bugs. 相似文献
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Hennigs Jan K. Lüneburg Nicole Stage Annett Schmitz Melanie Körbelin Jakob Harbaum Lars Matuszcak Christiane Mienert Julia Bokemeyer Carsten Böger Rainer H. Kiefmann Rainer Klose Hans 《Purinergic signalling》2019,15(3):299-311
Purinergic Signalling - Dysfunction of the pulmonary endothelium is associated with most lung diseases. Extracellular nucleotides modulate a plethora of endothelial functions in the lung such as... 相似文献
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Andreas Hoffmann Christiane Haas Stefan Hennig Kai Ostermann Thomas Bley Christian Lser Thomas Walther 《Engineering in Life Science》2019,19(6):400-411
Microbial consortia can be used to catalyze complex biotransformations. Tools to control the behavior of these consortia in a technical environment are currently lacking. In the present study, a synthetic biology approach was used to build a model consortium of two Saccharomyces cerevisiae strains where growth and expression of the fluorescent marker protein EGFP by the receiver strain is controlled by the concentration of α‐factor pheromone, which is produced by the emitter strain. We have developed a quantitative experimental and theoretical framework to describe population dynamics in the model consortium. We measured biomass growth and metabolite production in controlled bioreactor experiments, and used flow cytometry to monitor changes of the subpopulations and protein expression under different cultivation conditions. This dataset was used to parameterize a segregated mathematical model, which took into account fundamental growth processes, pheromone‐induced growth arrest and EGFP production, as well as pheromone desensitization after extended exposure. The model was able to predict the growth dynamics of single‐strain cultures and the consortium quantitatively and provides a basis for using this approach in actual biotransformations. 相似文献
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Jünemann C Song Y Bassili G Goergen D Henke J Niepmann M 《The Journal of biological chemistry》2007,282(1):132-141
Certain viral and cellular mRNAs initiate translation cap-independently at internal ribosome entry site (IRES) elements. Picornavirus IRES elements are widely used in dicistronic or multicistronic vectors in gene therapy, virus replicon systems, and analysis of IRES function. In such vectors, expression of the upstream gene often serves as internal control to standardize the readings of IRES-driven downstream reporter activity. Picornaviral IRES elements translate optimally at up to 120 mM K(+) concentration, whereas genes used as upstream reporters usually have lower salt optima when present in monocistronic mRNAs. However, here we show that such reporter genes are efficiently translated at higher K(+) concentrations when placed upstream of a functional picornavirus IRES. This translation enhancement occurs in cis, is independent of the nature of the first reporter and of second reporter translation, and is conferred by the IRESs of picornaviruses but not of hepatitis C virus. A defective picornavirus IRES with a deletion killing IRES activity but leaving the binding site for initiation factor eIF4G intact retains translation enhancement activity. Translation enhancement on a capped mRNA is disabled by m(7)GDP. In addition, the C-terminal fragment of eIF4G can confer translation enhancement also on uncapped mRNA. We conclude that whenever eIF4F has been captured to a dicistronic mRNA by binding to a picornavirus IRES via its eIF4G moiety, it can be provided in cis to the 5'-end of the RNA and there stimulate translation initiation, either by binding to the cap nucleotide using its eIF4E moiety or by binding to the RNA cap-independently using its eIF4G moiety. 相似文献
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Mochel F Charles P Seguin F Barritault J Coussieu C Perin L Le Bouc Y Gervais C Carcelain G Vassault A Feingold J Rabier D Durr A 《PloS one》2007,2(7):e647
Huntington disease (HD) is a fatal neurodegenerative disorder, with no effective treatment. The pathogenic mechanisms underlying HD has not been elucidated, but weight loss, associated with chorea and cognitive decline, is a characteristic feature of the disease that is accessible to investigation. We, therefore, performed a multiparametric study exploring body weight and the mechanisms of its loss in 32 presymptomatic carriers and HD patients in the early stages of the disease, compared to 21 controls. We combined this study with a multivariate statistical analysis of plasma components quantified by proton nuclear magnetic resonance ((1)H NMR) spectroscopy. We report evidence of an early hypermetabolic state in HD. Weight loss was observed in the HD group even in presymptomatic carriers, although their caloric intake was higher than that of controls. Inflammatory processes and primary hormonal dysfunction were excluded. (1)H NMR spectroscopy on plasma did, however, distinguish HD patients at different stages of the disease and presymptomatic carriers from controls. This distinction was attributable to low levels of the branched chain amino acids (BCAA), valine, leucine and isoleucine. BCAA levels were correlated with weight loss and, importantly, with disease progression and abnormal triplet repeat expansion size in the HD1 gene. Levels of IGF1, which is regulated by BCAA, were also significantly lower in the HD group. Therefore, early weight loss in HD is associated with a systemic metabolic defect, and BCAA levels may be used as a biomarker, indicative of disease onset and early progression. The decreased plasma levels of BCAA may correspond to a critical need for Krebs cycle energy substrates in the brain that increased metabolism in the periphery is trying to provide. 相似文献