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排序方式: 共有125条查询结果,搜索用时 629 毫秒
81.
Kanno T Bucher E Daxinger L Huettel B Böhmdorfer G Gregor W Kreil DP Matzke M Matzke AJ 《Nature genetics》2008,40(5):670-675
RNA-directed DNA methylation (RdDM) is a process in which dicer-generated small RNAs guide de novo cytosine methylation at the homologous DNA region. To identify components of the RdDM machinery important for Arabidopsis thaliana development, we targeted an enhancer active in meristems for methylation, which resulted in silencing of a downstream GFP reporter gene. This silencing system also features secondary siRNAs, which trigger methylation that spreads beyond the targeted enhancer region. A screen for mutants defective in meristem silencing and enhancer methylation retrieved six dms complementation groups, which included the known factors DRD1 (ref. 3; a SNF2-like chromatin-remodeling protein) and Pol IVb subunits. Additionally, we identified a previously unknown gene DMS3 (At3g49250), encoding a protein similar to the hinge-domain region of structural maintenance of chromosomes (SMC) proteins. This finding implicates a putative chromosome architectural protein that can potentially link nucleic acids in facilitating an RNAi-mediated epigenetic modification involving secondary siRNAs and spreading of DNA methylation. 相似文献
82.
Bio-scaffolds which are most commonly open celled porous structures are increasingly used for tissue engineering and regenerative medicine. A number of studies have shown that the bulk properties of such irregular structures are poorly modeled using idealized unit cell approaches. The paper therefore uses novel image based meshing techniques to explore both fluid flow and bulk structural properties of a bone scaffold, as accurate modeling of bio-scaffolds with non-uniform cellular structures is very important for the development of optimal scaffolds for tissue engineering application. In this study, a porous hydroxyapatite/tricalcium phosphate (HA/TCP) bone scaffold has been scanned in a Micro-CT scanner, and converted into a volumetric mesh using image processing software developed by the authors. The resulting mesh was then exported to commercial FEA and CFD solvers for analysis. Initial FEA and CFD studies have shown promising results and have highlighted the importance of accurate modeling to understand how microstructures influence the mechanical property of the scaffold, and to analyze flow regimes through the sample. The work highlights the potential use of image based meshing for the ad hoc characterization of scaffolds as well as for assisting in the design of scaffolds with tailored strength, stiffness, and transport properties. 相似文献
83.
Ribot JC debarros A Silva-Santos B 《Cellular and molecular life sciences : CMLS》2011,68(14):2345-2355
T cell activation requires the integration of signals that arise from various types of receptors. Although TCR triggering
is a necessary condition, it is often not sufficient to induce full T-cell activation, as reflected in cell proliferation
and cytokine secretion. This has been firmly demonstrated for conventional αβ T cells, for which a large panel of costimulatory
receptors has been identified. By contrast, the area remains more obscure for unconventional, innate-like γδ T cells, as the
literature has been scarce and at times contradictory. Here we review the current state of the art on the costimulatory requirements
of γδ T cell activation. We highlight the roles of members of the immunoglobulin (like CD28 or JAML) or tumour necrosis factor
receptor (like CD27) superfamilies of coreceptors, but also of more atypical costimulatory molecules, such as NKG2D or CD46.
Finally, we identify various areas where our knowledge is still markedly insufficient, hoping to provoke future research on
γδ T cell costimulation. 相似文献
84.
Goudie DR D'Alessandro M Merriman B Lee H Szeverényi I Avery S O'Connor BD Nelson SF Coats SE Stewart A Christie L Pichert G Friedel J Hayes I Burrows N Whittaker S Gerdes AM Broesby-Olsen S Ferguson-Smith MA Verma C Lunny DP Reversade B Lane EB 《Nature genetics》2011,43(4):365-369
Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving scars. High-throughput genomic sequencing of a conservative estimate (24.2 Mb) of the disease locus on chromosome 9 using exon array capture identified independent mutations in TGFBR1 in three unrelated families. Subsequent dideoxy sequencing of TGFBR1 identified 11 distinct monoallelic mutations in 18 affected families, firmly establishing TGFBR1 as the causative gene. The nature of the sequence variants, which include mutations in the extracellular ligand-binding domain and a series of truncating mutations in the kinase domain, indicates a clear genotype-phenotype correlation between loss-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer. 相似文献
85.
86.
Norman PJ Abi-Rached L Gendzekhadze K Korbel D Gleimer M Rowley D Bruno D Carrington CV Chandanayingyong D Chang YH Crespí C Saruhan-Direskeneli G Fraser PA Hameed K Kamkamidze G Koram KA Layrisse Z Matamoros N Milà J Park MH Pitchappan RM Ramdath DD Shiau MY Stephens HA Struik S Verity DH Vaughan RW Tyan D Davis RW Riley EM Ronaghi M Parham P 《Nature genetics》2007,39(9):1092-1099
Interactions of killer cell immunoglobulin-like receptors (KIRs) with major histocompatibility complex (MHC) class I ligands diversify natural killer cell responses to infection. By analyzing sequence variation in diverse human populations, we show that the KIR3DL1/S1 locus encodes two lineages of polymorphic inhibitory KIR3DL1 allotypes that recognize Bw4 epitopes of protein">HLA-A and HLA-B and one lineage of conserved activating KIR3DS1 allotypes, also implicated in Bw4 recognition. Balancing selection has maintained these three lineages for over 3 million years. Variation was selected at D1 and D2 domain residues that contact HLA class I and at two sites on D0, the domain that enhances the binding of KIR3D to HLA class I. HLA-B variants that gained Bw4 through interallelic microconversion are also products of selection. A worldwide comparison uncovers unusual KIR3DL1/S1 evolution in modern sub-Saharan Africans. Balancing selection is weak and confined to D0, KIR3DS1 is rare and KIR3DL1 allotypes with similar binding sites predominate. Natural killer cells express the dominant KIR3DL1 at a high frequency and with high surface density, providing strong responses to cells perturbed in Bw4 expression. 相似文献
87.
Valente EM Silhavy JL Brancati F Barrano G Krishnaswami SR Castori M Lancaster MA Boltshauser E Boccone L Al-Gazali L Fazzi E Signorini S Louie CM Bellacchio E;International Joubert Syndrome Related Disorders Study Group Bertini E Dallapiccola B Gleeson JG 《Nature genetics》2006,38(6):623-625
Joubert syndrome-related disorders (JSRD) are a group of syndromes sharing the neuroradiological features of cerebellar vermis hypoplasia and a peculiar brainstem malformation known as the 'molar tooth sign'. We identified mutations in the CEP290 gene in five families with variable neurological, retinal and renal manifestations. CEP290 expression was detected mostly in proliferating cerebellar granule neuron populations and showed centrosome and ciliary localization, linking JSRDs to other human ciliopathies. 相似文献
88.
Stoetzel C Laurier V Davis EE Muller J Rix S Badano JL Leitch CC Salem N Chouery E Corbani S Jalk N Vicaire S Sarda P Hamel C Lacombe D Holder M Odent S Holder S Brooks AS Elcioglu NH Silva ED Da Silva E Rossillion B Sigaudy S de Ravel TJ Lewis RA Leheup B Verloes A Amati-Bonneau P Mégarbané A Poch O Bonneau D Beales PL Mandel JL Katsanis N Dollfus H 《Nature genetics》2006,38(5):521-524
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy. Although nine BBS genes have been cloned, they explain only 40-50% of the total mutational load. Here we report a major new BBS locus, BBS10, that encodes a previously unknown, rapidly evolving vertebrate-specific chaperonin-like protein. We found BBS10 to be mutated in about 20% of an unselected cohort of families of various ethnic origins, including some families with mutations in other BBS genes, consistent with oligogenic inheritance. In zebrafish, mild suppression of bbs10 exacerbated the phenotypes of other bbs morphants. 相似文献
89.
通过对无缝桥引板资料的统计分析,通过综述国内外的引板构造及工程应用、引板-土相互作用以及该相互作用对无缝桥力学性能的影响.结果表明,在我国无缝桥中面板式引板应用最广泛,斜埋入式引板和Z形引板也有应用;常采用设置单层纵向直线钢筋的无缝桥-引板连接构造.计算面板式引板时需要考虑板下填土的竖向支承与切向约束,搭板计算方法不适用;尚未提出关于埋入式引板和Z形引板的计算方法.无缝桥-引板连接构造处及引板末端对应的路面是最易出现开裂和沉降的位置.路面平整度是分析引板-土相互作用的关键控制指标.需关注引板-土相互作用对无缝桥边跨主梁弯矩、柱顶剪力、主梁和引板拉应力、纵向基频及极限长度影响. 相似文献
90.
Protein coats deform flat lipid membranes into buds and capture membrane proteins to form transport vesicles. The assembly/disassembly cycle of the COPI coat on Golgi membranes is coupled to the GTP/GDP cycle of the small G protein Arf1. At the heart of this coupling is the specific interaction of membrane-bound Arf1-GTP with coatomer, a complex of seven proteins that forms the building unit of the COPI coat. Although COPI coat disassembly requires the catalysis of GTP hydrolysis in Arf1 by a specific GTPase-activating protein (ArfGAP1), the precise timing of this reaction during COPI vesicle formation is not known. Using time-resolved assays for COPI dynamics on liposomes of controlled size, we show that the rate of ArfGAP1-catalysed GTP hydrolysis in Arf1 and the rate of COPI disassembly increase over two orders of magnitude as the curvature of the lipid bilayer increases and approaches that of a typical transport vesicle. This leads to a model for COPI dynamics in which GTP hydrolysis in Arf1 is organized temporally and spatially according to the changes in lipid packing induced by the coat. 相似文献