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71.
Jerri Caldeira Jeremiah Bustos Julianne Peabody Bryce Chackerian David S. Peabody 《PloS one》2015,10(10)
The possibility of a contraceptive vaccine targeting human chorionic gonadotropin has long been recognized, but never fully realized. Here we describe an epitope-specific approach based on immunogenic display of hCG-derived peptides on virus-like particles of RNA bacteriophage. A number of recombinant VLPs were constructed, each displaying a different hCG-derived peptide. Some were taken from the disordered C-terminal tail of the hormone, another came from an internal loop, and yet another was an epitope mimic produced by affinity-selection on an hCG-neutralizing antibody target. Immunization of mice with some VLPs yielded antisera that bound the hormone and neutralized hCG biological activity. 相似文献
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Yaroslav Staroseletz Sergey Nechaev Elena Bichenkova Richard A. Bryce Catherine Watson Valentin Vlassov Marina Zenkova 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(3):705-725
Background
While the RNA world hypothesis is widely accepted, it is still far from complete: the existence of self-replicating ribozyme, consisting of potentially hundreds of nucleotides, is a core assumption for the majority of RNA world models. The appearance of such long RNA molecules under prebiotic conditions is not self-evident. Recombination seems to be a plausible way of creating RNA diversity, resulting in the appearance of functional RNAs, capable of self-replicating.Methods
We report here on the study of recombination process modelled with two 96 nts RNA fragments. Detection of recombination products was performed with RT-PCR followed by TA-cloning and Sanger sequencing.Results
A wide range of recombinant products was detected. We found that (i) the most efficient ligation was observed for RNA species forming bulges or internal loops, with ligation partners located within the loop; (ii) a strong preference was observed for formation of a few types of major products with a large variety of minor products; (iii) ligation could occur with participation of either 2′,3′-cyclophosphate or 5′-ppp; (iv) the presence of key reaction components, i.e. 5′ppp-RNAs, enabled the formation of additional types of product; (v) molecular dynamics simulations of one of the most abundant products suggests that the ligation results in a preferable formation of 2′-5′- rather than 3′-5′-linkages.Conclusions
The study demonstrates regularities of new RNA molecules formation with non-enzymatic recombination process.General significance
Our findings provide new data supporting the RNA World hypothesis and show the way of new RNA sequences emergence under prebiotic conditions. 相似文献74.
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77.
Nakrieko KA Welch I Dupuis H Bryce D Pajak A St Arnaud R Dedhar S D'Souza SJ Dagnino L 《Molecular biology of the cell》2008,19(4):1462-1473
Integrin-linked kinase (ILK) is key for cell survival, migration, and adhesion, but little is known about its role in epidermal development and homeostasis in vivo. We generated mice with conditional inactivation of the Ilk gene in squamous epithelia. These mice die perinatally and exhibit skin blistering and severe defects in hair follicle morphogenesis, including greatly reduced follicle numbers, failure to progress beyond very early developmental stages, and pronounced defects in follicular keratinocyte proliferation. ILK-deficient epidermis shows abnormalities in adhesion to the basement membrane and in differentiation. ILK-deficient cultured keratinocytes fail to attach and spread efficiently and exhibit multiple abnormalities in actin cytoskeletal organization. Ilk gene inactivation in cultured keratinocytes causes impaired ability to form stable lamellipodia, to directionally migrate, and to polarize. These defects are accompanied by abnormal distribution of active Cdc42 to cell protrusions, as well as reduced activation of Rac1 upon induction of cell migration in scraped keratinocyte monolayers. Significantly, alterations in cell spreading and forward movement in single cells can be rescued by expression of constitutively active Rac1 or RhoG. Our studies underscore a central and distinct role for ILK in hair follicle development and in polarized cell movements, two key aspects of epithelial morphogenesis and function. 相似文献
78.
Randell T. Libby Katharine A. Hagerman Victor V. Pineda Rachel Lau Diane H. Cho Sandy L. Baccam Michelle M. Axford John D. Cleary James M. Moore Bryce L. Sopher Stephen J. Tapscott Galina N. Filippova Christopher E. Pearson Albert R. La Spada 《PLoS genetics》2008,4(11)
At least 25 inherited disorders in humans result from microsatellite repeat expansion. Dramatic variation in repeat instability occurs at different disease loci and between different tissues; however, cis-elements and trans-factors regulating the instability process remain undefined. Genomic fragments from the human spinocerebellar ataxia type 7 (SCA7) locus, containing a highly unstable CAG tract, were previously introduced into mice to localize cis-acting “instability elements,” and revealed that genomic context is required for repeat instability. The critical instability-inducing region contained binding sites for CTCF—a regulatory factor implicated in genomic imprinting, chromatin remodeling, and DNA conformation change. To evaluate the role of CTCF in repeat instability, we derived transgenic mice carrying SCA7 genomic fragments with CTCF binding-site mutations. We found that CTCF binding-site mutation promotes triplet repeat instability both in the germ line and in somatic tissues, and that CpG methylation of CTCF binding sites can further destabilize triplet repeat expansions. As CTCF binding sites are associated with a number of highly unstable repeat loci, our findings suggest a novel basis for demarcation and regulation of mutational hot spots and implicate CTCF in the modulation of genetic repeat instability. 相似文献
79.
Atatreh N Stojkoski C Smith P Booker GW Dive C Frenkel AD Freeman S Bryce RA 《Bioorganic & medicinal chemistry letters》2008,18(3):1217-1222
Src signalling and transduction are directly involved in cell growth, cell cycle, malignant transformation and cell migration, providing therapeutic opportunities through inhibition of Src. Here we report virtual screening for novel compounds that inhibit the Src-SH3 protein-protein interaction with a proline-rich peptide ligand. Computational docking of the ZINC compound database was performed using GOLD. Top-scoring compounds were assayed using a fluorescence polarization-based assay. A benzoquinoline derivative showed micromolar inhibition of binding between Src-SH3 and the proline-rich peptide. Several analogues were subsequently assayed showing the requirement of a linker between the benzoquinoline and phenyl rings, and electron donating substituents on the phenyl ring. 相似文献
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