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101.
The RNA helicase Upf1 is a multifaceted eukaryotic enzyme involved in DNA replication, telomere metabolism and several mRNA degradation pathways. Upf1 plays a central role in nonsense-mediated mRNA decay (NMD), a surveillance process in which it links premature translation termination to mRNA degradation with its conserved partners Upf2 and Upf3. In human, both the ATP-dependent RNA helicase activity and the phosphorylation of Upf1 are essential for NMD. Upf1 activation occurs when Upf2 binds its N-terminal domain, switching the enzyme to the active form. Here, we uncovered that the C-terminal domain of Upf1, conserved in higher eukaryotes and containing several essential phosphorylation sites, also inhibits the flanking helicase domain. With different biochemical approaches we show that this domain, named SQ, directly interacts with the helicase domain to impede ATP hydrolysis and RNA unwinding. The phosphorylation sites in the distal half of the SQ domain are not directly involved in this inhibition. Therefore, in the absence of multiple binding partners, Upf1 is securely maintained in an inactive state by two intramolecular inhibition mechanisms. This study underlines the tight and intricate regulation pathways required to activate multifunctional RNA helicases like Upf1. 相似文献
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103.
Carla Bazzicalupi Marta Ferraroni Anna Rita Bilia Francesca Scheggi Paola Gratteri 《Nucleic acids research》2013,41(1):632-638
The first crystal structure of human telomeric DNA in complex with the natural alkaloid berberine, produced by different plant families and used in folk medicine for millennia, was solved by X-ray diffraction method. The G-quadruplex unit features all-parallel strands. The overall folding assumed by DNA is the same found in previously reported crystal structures. Similarly to previously reported structures the ligand molecules were found to be stacked onto the external 5′ and 3′-end G-tetrads. However, the present crystal structure highlighted for the first time, the presence of two berberine molecules in the two binding sites, directly interacting with each tetrad. As a consequence, our structural data point out a 2:1 ligand to G-tetrad molar ratio, which has never been reported before in a telomeric intramolecular quadruplex structure. 相似文献
104.
Aroldo Cupello Mario Di Braccio Elena Gatta Giancarlo Grossi Periklis Nikas Francesca Pellistri Mauro Robello 《Neurochemical research》2013,38(12):2453-2462
GABAA receptor mediated inhibition plays an important role in modulating the input/output dynamics of cerebellum. A characteristic of cerebellar GABAA receptors is the presence in cerebellar granule cells of subunits such as α6 and δ which give insensitivity to classical benzodiazepines. In fact, cerebellar GABAA receptors have generally been considered a poor model for testing drugs which potentially are active at the benzodiazepine site. In this overview we show how rat cerebellar granule cells in culture may be a useful model for studying new benzodiazepine site agonists. This is based on the pharmacological separation of diazepam-sensitive α1 β2/3 γ2 receptors from those which are diazepam-insensitive and contain the α6 subunit. This is achieved by utilizing furosemide/Zn2+ which block α6 containing and incomplete receptors. 相似文献
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Alberto Addis Francesca Fabiano Valentina Delogu 《Invertebrate reproduction & development.》2013,57(2):142-155
The reproductive systems of adults and larvae of Lightiella magdalenina were examined. Lightiella magdalenina, similar to the best-known cephalocarida species Hutchinsoniella macracantha, is a simultaneous hermaphrodite. Although the morphology of their reproductive system is similar, L. magdalenina differs from H. macracantha in exhibiting reduced fecundity: it lays one egg, not two, per reproductive event. This is due to asynchronous development of the oocytes inside the paired female reproductive structures, which determines the maturation of a single egg at a time. The reduced fecundity of L. magdalenina could be offset by the precocious release of oocytes from the germarium, which begins the vitellogenetic process during the last larval stages. Due to this process, after their last moult, reproductive adults can have a large number of advanced vitellogenic oocytes, reducing the time required for their maturation. A possible adaptive relationship between the halved fecundity with pre- and post-hatching parental care is discussed. 相似文献
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108.
Alfonso De Simone Francesca Stanzione Daniela Marasco 《Journal of biomolecular structure & dynamics》2013,31(5):441-452
Human prion diseases are neurodegenerative disorders associated to the misfolding of the prion protein (PrP). Common features of prion disorders are the fibrillar amyloid deposits and the formation of prefibrillar oligomeric species also suggested as the origin of cytotoxicity associated with diseases. Although the process of PrP misfolding has been extensively investigated, many crucial aspects of this process remain unclear. We have here carried out a molecular dynamics study to evaluate the intrinsic dynamics of PrP β-sheet, a region that is believed to play a crucial role in prion aggregation. Moreover, as this region mediates protein association in dimeric assemblies frequently observed in prion crystallographic investigations, we also analyzed the dynamics of these intermolecular interactions. The extensive sampling of replica exchange shows that the native antiparallel β-structure of the prion is endowed with a remarkable stability. Therefore, upon unfolding, the persistence of a structured β-region may seed molecular association and influence the subsequent phases of the aggregation process. The analysis of the four-stranded β-sheet detected in the dimeric assemblies of PrP shows a tendency of this region to form dynamical structured states. The impact on the β-sheet structure and dynamics of disease associated point mutations has also been evaluated. 相似文献
109.
Francesca Borghini Andrea Colacevich Steven Arthur Loiselle Roberto Bargagli 《Polar Biology》2013,36(8):1147-1160
Lakes are among the most productive and biodiverse ecosystems in Antarctica, and they behave as important indicators of local climatic and environmental changes. However, few studies have focused on the local drivers of short-term temporal variability in lacustrine biogeochemical variables. In the present study, measurements of physical, chemical, biological and optical characteristics of the shallow endorheic Lake 14 at Edmonson Point (74.33° S, 165.13° E) were made over the ice-free period in December 2006. A significant variation in most variables was observed. Possible drivers for these changes were the loss of the ice cover, an increase in solar irradiance, a change in photosynthetic activity and the evaporative loss of water. By removing relative changes due to evaporative losses, new insights were gained into the driving factors controlling the biogeochemistry and primary productivity in the shallow Antarctic lake. In particular, a decrease in phytoplankton biomass was observed and was probably linked to photoinhibition as revealed by an increase in photoprotective pigments. The absorbance by dissolved organic matter, when weighted with respect to evaporative loss, shows an overall reduction in humic-like absorption, most likely linked to photodegradation. 相似文献