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31.
K A Valentine-Braun M D Hollenberg E Fraser J K Northup 《Archives of biochemistry and biophysics》1987,259(2):262-282
Using as a starting material either a detergent extract or a protein fraction eluted from membranes with ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid, we have isolated from human placental membranes a major substrate for the epidermal growth factor (urogastrone) receptor kinase (EGF kinase). The substrate was isolated both in an intact form, having a molecular mass of approximately 38-kDa (p38), and in a 35-kDa form (p35) representing a proteolytic cleavage product of p38. Both p38 and p35 cross-reacted with antibodies directed against bovine retinal transducin, but did not cross-react with antibodies directed against the 35-kDa beta subunit of human placental G-protein. Antisera directed against the placental EGF kinase substrate failed to react with either bovine or human placental src kinase substrate, p36. Conversely, antisera directed against p36 reacted only poorly with placental p38 or p35. Although p38 had a blocked amino terminus that precluded sequence analysis, p35 yielded an N-terminal sequence that was identical with residues 13-36 of human lipocortin. Our data clearly distinguish p38 from the previously described intestinal calcium binding protein calpactin I or p36 that is also a tyrosine kinase substrate, and our work points to a close relationship (if not identity) between p35 and a 35-kDa EGF receptor kinase substrate previously characterized in A431 cells. We conclude that p38 and p35, which very likely represent human placental lipocortin, may share only limited epitope homology with transducin alpha subunit; however, the possibility that p38, along with intestinal p36 and with a family of related calcium binding proteins, may, like transducin, play a role in receptor-mediated transmembrane signaling is discussed. 相似文献
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Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis 下载免费PDF全文
Rothbächer U Laurent MN Deardorff MA Klein PS Cho KW Fraser SE 《The EMBO journal》2000,19(5):1010-1022
Dishevelled (Dsh) induces a secondary axis and can translocate to the membrane when activated by Frizzleds; however, dominant-negative approaches have not supported a role for Dsh in primary axis formation. We demonstrate that the Dsh protein is post-translationally modified at the dorsal side of the embryo: timing and position of this regulation suggests a role of Dsh in dorsal-ventral patterning in Xenopus. To create functional links between these properties of Dsh we analyzed the influence of endogenous Frizzleds and the Dsh domain dependency for these characteristics. Xenopus Frizzleds phosphorylate and translocate Xdsh to the membrane irrespective of their differential ectopic axes inducing abilities, showing that translocation is insufficient for axis induction. Dsh deletion analysis revealed that axis inducing abilities did not segregate with Xdsh membrane association. The DIX region and a short stretch at the N-terminus of the DEP domain are necessary for axis induction while the DEP region is required for Dsh membrane association and its phosphorylation. In addition, Dsh forms homomeric complexes in embryos suggesting that multimerization is important for its proper function. 相似文献
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Moya M. Smith Zerina Johanson Thomas Butts Rolf Ericsson Melinda Modrell Frank J. Tulenko Marcus C. Davis Gareth J. Fraser 《Proceedings. Biological sciences / The Royal Society》2015,282(1805)
Ray-finned fishes (Actinopterygii) are the dominant vertebrate group today (+30 000 species, predominantly teleosts), with great morphological diversity, including their dentitions. How dental morphological variation evolved is best addressed by considering a range of taxa across actinopterygian phylogeny; here we examine the dentition of Polyodon spathula (American paddlefish), assigned to the basal group Acipenseriformes. Although teeth are present and functional in young individuals of Polyodon, they are completely absent in adults. Our current understanding of developmental genes operating in the dentition is primarily restricted to teleosts; we show that shh and bmp4, as highly conserved epithelial and mesenchymal genes for gnathostome tooth development, are similarly expressed at Polyodon tooth loci, thus extending this conserved developmental pattern within the Actinopterygii. These genes map spatio-temporal tooth initiation in Polyodon larvae and provide new data in both oral and pharyngeal tooth sites. Variation in cellular intensity of shh maps timing of tooth morphogenesis, revealing a second odontogenic wave as alternate sites within tooth rows, a dental pattern also present in more derived actinopterygians. Developmental timing for each tooth field in Polyodon follows a gradient, from rostral to caudal and ventral to dorsal, repeated during subsequent loss of teeth. The transitory Polyodon dentition is modified by cessation of tooth addition and loss. As such, Polyodon represents a basal actinopterygian model for the evolution of developmental novelty: initial conservation, followed by tooth loss, accommodating the adult trophic modification to filter-feeding. 相似文献
36.
James F. Dwyer Joan L. Morrison James D. Fraser 《The Journal of wildlife management》2012,76(4):857-862
Management of crested caracaras (Caracara cheriway), focuses on nests identified during surveys. If no nests are found, management can be suspended. Thus, false negatives can have substantial consequences. We surveyed 49 breeding territories to assess factors with the potential to cause false negatives in detecting nests of crested caracaras and in observing adult birds. The probability that a nest would be detected on any given visit increased by about 0.5% for each hour of observer experience up to about 70 hours (our maximum). Experience did not affect the probability of observing an adult. The probability of detecting a caracara nest or observing an adult caracara decreased by 2.0–3.5% each hour after sunrise that a visit began. If visibility during any portion of a visit was obscured by fog or rain, the probability of detecting a nest decreased by as much as 60%, and the probability of observing an adult caracara decreased by about 50%. We provide a tool managers can use to calculate the likelihood of successful surveys. We recommend that managers disregard negative results from surveys conducted under conditions that are unlikely to yield positive results, and repeat those surveys under better conditions. © 2011 The Wildlife Society. 相似文献
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Guoliang Wei Zidong Wang James Lam Karl Fraser Ganti Prasada Rao Xiaohui Liu 《Mathematical biosciences》2009,(2):73-80
This paper addresses the robust filtering problem for a class of linear genetic regulatory networks (GRNs) with stochastic disturbances, parameter uncertainties and time delays. The parameter uncertainties are assumed to reside in a polytopic region, the stochastic disturbance is state-dependent described by a scalar Brownian motion, and the time-varying delays enter into both the translation process and the feedback regulation process. We aim to estimate the true concentrations of mRNA and protein by designing a linear filter such that, for all admissible time delays, stochastic disturbances as well as polytopic uncertainties, the augmented state estimation dynamics is exponentially mean square stable with an expected decay rate. A delay-dependent linear matrix inequality (LMI) approach is first developed to derive sufficient conditions that guarantee the exponential stability of the augmented dynamics, and then the filter gains are parameterized in terms of the solution to a set of LMIs. Note that LMIs can be easily solved by using standard software packages. A simulation example is exploited in order to illustrate the effectiveness of the proposed design procedures. 相似文献
39.
With an ecological-evolutionary perspective increasingly applied toward the conservation and management of endangered or exploited species, the genetic estimation of effective population size (Ne) has proliferated. Based on a comprehensive analysis of empirical literature from the past two decades, we asked: (i) how often do studies link Ne to the adult census population size (N)? (ii) To what extent is Ne correctly linked to N? (iii) How readily is uncertainty accounted for in both Ne and N when quantifying Ne/N ratios? and (iv) how frequently and to what degree might errors in the estimation of Ne or N affect inferences of Ne/N ratios? We found that only 20% of available Ne estimates (508 of 2617; 233 studies) explicitly attempted to link Ne and N; of these, only 31% (160 of 508) correctly linked Ne and N. Moreover, only 7% (41 of 508) of Ne/N ratios (correctly linked or not) reported confidence intervals for both Ne and N; for those cases where confidence intervals were reported for Ne only, 31% of Ne/N ratios overlapped with 1, of which more than half also reached below Ne/N = 0.01. Uncertainty in Ne/N ratios thus sometimes spanned at least two orders of magnitude. We conclude that the estimation of Ne/N ratios in natural populations could be significantly improved, discuss several options for doing so, and briefly outline some future research directions. 相似文献
40.
Hedieh Shahpasandzadeh Blagovesta Popova Alexandra Kleinknecht Paul E. Fraser Tiago F. Outeiro Gerhard H. Braus 《The Journal of biological chemistry》2014,289(45):31224-31240
Parkinson disease is associated with the progressive loss of dopaminergic neurons from the substantia nigra. The pathological hallmark of the disease is the accumulation of intracytoplasmic inclusions known as Lewy bodies that consist mainly of post-translationally modified forms of α-synuclein. Whereas phosphorylation is one of the major modifications of α-synuclein in Lewy bodies, sumoylation has recently been described. The interplay between α-synuclein phosphorylation and sumoylation is poorly understood. Here, we examined the interplay between these modifications as well as their impact on cell growth and inclusion formation in yeast. We found that α-synuclein is sumoylated in vivo at the same sites in yeast as in human cells. Impaired sumoylation resulted in reduced yeast growth combined with an increased number of cells with inclusions, suggesting that this modification plays a protective role. In addition, inhibition of sumoylation prevented autophagy-mediated aggregate clearance. A defect in α-synuclein sumoylation could be suppressed by serine 129 phosphorylation by the human G protein-coupled receptor kinase 5 (GRK5) in yeast. Phosphorylation reduced foci formation, alleviated yeast growth inhibition, and partially rescued autophagic α-synuclein degradation along with the promotion of proteasomal degradation, resulting in aggregate clearance in the absence of a small ubiquitin-like modifier. These findings suggest a complex interplay between sumoylation and phosphorylation in α-synuclein aggregate clearance, which may open new horizons for the development of therapeutic strategies for Parkinson disease. 相似文献