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排序方式: 共有269条查询结果,搜索用时 15 毫秒
41.
Karina Tuz Ruxandra Bachmann-Gagescu Diana?R. O’Day Kiet Hua Christine?R. Isabella Ian?G. Phelps Allan?E. Stolarski Brian?J. O’Roak Jennifer?C. Dempsey Charles Lourenco Abdulrahman Alswaid Carsten?G. B?nnemann Livija Medne Sheela Nampoothiri Zornitza Stark Richard?J. Leventer Meral Top?u Ali Cansu Sujatha Jagadeesh Stephen Done Gisele?E. Ishak Ian?A. Glass Jay Shendure Stephan?C.F. Neuhauss Chad?R. Haldeman-Englert Dan Doherty Russell?J. Ferland 《American journal of human genetics》2014,94(1):62-72
Joubert syndrome (JBTS) is a recessive ciliopathy in which a subset of affected individuals also have the skeletal dysplasia Jeune asphyxiating thoracic dystrophy (JATD). Here, we have identified biallelic truncating CSPP1 (centrosome and spindle pole associated protein 1) mutations in 19 JBTS-affected individuals, four of whom also have features of JATD. CSPP1 mutations explain ∼5% of JBTS in our cohort, and despite truncating mutations in all affected individuals, the range of phenotypic severity is broad. Morpholino knockdown of cspp1 in zebrafish caused phenotypes reported in other zebrafish models of JBTS (curved body shape, pronephric cysts, and cerebellar abnormalities) and reduced ciliary localization of Arl13b, further supporting loss of CSPP1 function as a cause of JBTS. Fibroblasts from affected individuals with CSPP1 mutations showed reduced numbers of primary cilia and/or short primary cilia, as well as reduced axonemal localization of ciliary proteins ARL13B and adenylyl cyclase III. In summary, CSPP1 mutations are a major cause of the Joubert-Jeune phenotype in humans; however, the mechanism by which these mutations lead to both JBTS and JATD remains unknown. 相似文献
42.
Morello R Bertin TK Schlaubitz S Shaw CA Kakuru S Munivez E Hermanns P Chen Y Zabel B Lee B 《Journal of cellular physiology》2008,217(1):127-137
Wnt signaling pathways are regulated both at the intracellular and extracellular levels. During embryogenesis, the in vivo effects of the secreted frizzled-related protein (Sfrp) family of Wnt inhibitors are poorly understood. Here, we show that inactivation of Sfrp2 results in subtle limb defects in mice with mesomelic shortening and consistent shortening of all autopodal elements that is clinically manifested as brachydactyly. In addition, there is soft-tissue syndactyly of the hindlimb. The brachydactyly is caused by decreased chondrocyte proliferation and delayed differentiation in distal limb chondrogenic elements. These data suggest that Sfrp2 can regulate both chondrogenesis and regression of interdigital mesenchyme in distal limb. Sfrp2 can also repress canonical Wnt signaling by Wnt1, Wnt9a, and Wnt4 in vitro. Sfrp2-/- and TOPGAL/Sfrp2-/- mice have a mild increase in beta-catenin and beta-galactosidase staining, respectively, in some phalangeal elements. This however does not exclude a potential concurrent effect on non-canonical Wnt signaling in the growth plate. In combination with what is known about BMP and Wnt signaling in human brachydactylies, our data establish a critical role for Sfrp2 in proper distal limb formation and suggest SFPR2 could be a novel candidate gene for human brachy-syndactyly defects. 相似文献
43.
T Joseph VG Saipradeep GS Raghavan R Srinivasan A Rao S Kotte N Sivadasan 《Bioinformation》2012,8(12):578-580
TPX is a web-based PubMed search enhancement tool that enables faster article searching using analysis and exploration features. These features include identification of relevant biomedical concepts from search results with linkouts to source databases, concept based article categorization, concept assisted search and filtering, query refinement. A distinguishing feature here is the ability to add user-defined concept names and/or concept types for named entity recognition. The tool allows contextual exploration of knowledge sources by providing concept association maps derived from the MEDLINE repository. It also has a full-text search mode that can be configured on request to access local text repositories, incorporating entity co-occurrence search at sentence/paragraph levels. Local text files can also be analyzed on-the-fly. Availability: http://tpx.atc.tcs.com 相似文献
44.
The phylogeny and evolution of host choice in the Hippoboscoidea (Diptera) as reconstructed using four molecular markers 总被引:1,自引:0,他引:1
Hippoboscoidea is a superfamily of Diptera that contains the Glossinidae or tsetse flies, the Hippoboscidae or louse flies, and two families of bat flies, the Streblidae and the Nycteribiidae. We reconstruct the phylogenetic relationships within Hippoboscoidea using maximum parsimony and Bayesian methods based on nucleotide sequences from fragments of four genes: nuclear 28S ribosomal DNA and the CPSase domain of CAD, and mitochondrial 16S rDNA and cytochrome oxidase I. We recover monophyly for most of the presently recognized groups within Hippoboscoidea including the superfamily as a whole, the Hippoboscidae, the Nycteribiidae, the bat flies, and the Pupipara (=Hippoboscidae+Nycteribiidae+Streblidae), as well as several subfamilies within the constituent families. Streblidae appear to be paraphyletic. Our phylogenetic hypothesis is well supported and decisive in that most competing topological hypotheses for the Hippoboscoidea require significantly longer trees. We confirm a single shift from a free-living fly to a blood-feeding ectoparasite of vertebrates and demonstrate that at least two host shifts from mammals to birds have occurred. Wings have been repeatedly lost, but never regained. The hippoboscoid ancestor also evolved adenotrophic viviparity and our cladogram is consistent with a gradual reduction in the motility of the deposited final instar larvae from active burrowing in the soil to true pupiparity where adult females glue the puparium within the confines of bat roosts. 相似文献
45.
Dasgupta S Hu X Keizers PH Liu WM Luchinat C Nagulapalli M Overhand M Parigi G Sgheri L Ubbink M 《Journal of biomolecular NMR》2011,51(3):253-263
Calmodulin is a two-domain protein which in solution can adopt a variety of conformations upon reorientation of its domains.
The maximum occurrence (MO) of a set of calmodulin conformations that are representative of the overall conformational space
possibly sampled by the protein, has been calculated from the paramagnetism-based restraints. These restraints were measured
after inclusion of a lanthanide binding tag in the C-terminal domain to supplement the data obtained by substitution of three
paramagnetic lanthanide ions to the calcium ion in the second calcium binding loop of the N-terminal domain. The analysis
shows that the availability of paramagnetic restraints arising from metal ions placed on both domains, reduces the MO of the
conformations to different extents, thereby helping to identify those conformations that can be mostly sampled by the protein. 相似文献
46.
We reconstruct the regulatory network controlling commitment and sporulation of Physarum polycephalum from experimental results using a hierarchical Petri Net-based modelling and simulation framework. The stochastic Petri Net consistently describes the structure and simulates the dynamics of the molecular network as analysed by genetic, biochemical and physiological experiments within a single coherent model. The Petri Net then is extended to simulate time-resolved somatic complementation experiments performed by mixing the cytoplasms of mutants altered in the sporulation response, to systematically explore the network structure and to probe its dynamics. This reverse engineering approach presumably can be employed to explore other molecular or genetic signalling systems where the activity of genes or their products can be experimentally controlled in a time-resolved manner. 相似文献
47.
Diversity and Distribution of Planctomycetes and Related Bacteria in the Suboxic Zone of the Black Sea 总被引:2,自引:1,他引:1 下载免费PDF全文
John Kirkpatrick Brian Oakley Clara Fuchsman Sujatha Srinivasan James T. Staley James W. Murray 《Applied microbiology》2006,72(4):3079-3083
Samples from six depths of the Black Sea's suboxic zone were analyzed for 16S rRNA gene sequence information. A gradient in phylotype diversity was found. The distributions of known anaerobic ammonium oxidation (anammox) bacteria, many unknown Planctomycetes, and other phylotypes were examined in relation to the local nutrient and redox conditions. 相似文献
48.
Dona L Fleishaker Juan A Garcia Meijide Andriy Petrov Michael David Kohen Xin Wang Sujatha Menon Thomas C Stock Charles A Mebus James M Goodrich Howard B Mayer Bernhardt G Zeiher 《Arthritis research & therapy》2012,14(1):R11-11
Introduction
The purpose of this study was to determine whether maraviroc, a human CC chemokine receptor 5 (CCR5) antagonist, is safe and effective in the treatment of active rheumatoid arthritis (RA) in patients on background methotrexate (MTX).Methods
This phase IIa study comprised two distinct components: an open-label safety study of the pharmacokinetics (PK) of MTX in the presence of maraviroc, and a randomized, double-blind, placebo-controlled, proof-of-concept (POC) component. In the PK component, patients were randomized 1:1 to receive maraviroc 150 or 300 mg twice daily (BID) for four weeks. In the POC component, patients were randomized 2:1 to receive maraviroc 300 mg BID or placebo for 12 weeks. Patients were not eligible for inclusion in both components.Results
Sixteen patients were treated in the safety/PK component. Maraviroc was well tolerated and there was no evidence of drug-drug interaction with MTX. One hundred ten patients were treated in the POC component. The study was terminated after the planned interim futility analysis due to lack of efficacy, at which time 59 patients (38 maraviroc; 21 placebo) had completed their week 12 visit. There was no significant difference in the number of ACR20 responders between the maraviroc (23.7%) and placebo (23.8%) groups (treatment difference -0.13%; 90% CI -20.45, 17.70; P = 0.504). The most common all-causality treatment-emergent adverse events in the maraviroc group were constipation (7.8%), nausea (5.2%), and fatigue (3.9%).Conclusions
Maraviroc was generally well tolerated over 12 weeks; however, selective antagonism of CCR5 with maraviroc 300 mg BID failed to improve signs and symptoms in patients with active RA on background MTX.Trial Registration
ClinicalTrials.gov: NCT00427934 相似文献49.
50.