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排序方式: 共有139条查询结果,搜索用时 18 毫秒
31.
Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy 总被引:4,自引:0,他引:4
Nicot AS Toussaint A Tosch V Kretz C Wallgren-Pettersson C Iwarsson E Kingston H Garnier JM Biancalana V Oldfors A Mandel JL Laporte J 《Nature genetics》2007,39(9):1134-1139
Centronuclear myopathies are characterized by muscle weakness and abnormal centralization of nuclei in muscle fibers not secondary to regeneration. The severe neonatal X-linked form (myotubular myopathy) is due to mutations in the phosphoinositide phosphatase myotubularin (MTM1), whereas mutations in dynamin 2 (DNM2) have been found in some autosomal dominant cases. By direct sequencing of functional candidate genes, we identified homozygous mutations in amphiphysin 2 (BIN1) in three families with autosomal recessive inheritance. Two missense mutations affecting the BAR (Bin1/amphiphysin/RVS167) domain disrupt its membrane tubulation properties in transfected cells, and a partial truncation of the C-terminal SH3 domain abrogates the interaction with DNM2 and its recruitment to the membrane tubules. Our results suggest that mutations in BIN1 cause centronuclear myopathy by interfering with remodeling of T tubules and/or endocytic membranes, and that the functional interaction between BIN1 and DNM2 is necessary for normal muscle function and positioning of nuclei. 相似文献
32.
FMRP与TDG蛋白的相互作用 总被引:3,自引:0,他引:3
脆性X智力低下蛋白FMRP表达的缺乏可以导致最常见的遗传性智力低下疾病—脆性X综合征。用酵母双杂交体系筛选与FMRP相互作用的蛋白质,以期通过相互作用的蛋白质研究与FMRP相关的生化途径。从小鼠胚胎cDNA文库中得到一个与FMRP特异相互作用蛋白的cDNA(Genbank号af102857)。该cDNA编码的蛋白与人的G/T错配DNA胸腺嘧啶糖苷酶(hTDG)高度同源通过多种FMRP造反剪接异构体 相似文献
33.
Kämper J Kahmann R Bölker M Ma LJ Brefort T Saville BJ Banuett F Kronstad JW Gold SE Müller O Perlin MH Wösten HA de Vries R Ruiz-Herrera J Reynaga-Peña CG Snetselaar K McCann M Pérez-Martín J Feldbrügge M Basse CW Steinberg G Ibeas JI Holloman W Guzman P Farman M Stajich JE Sentandreu R González-Prieto JM Kennell JC Molina L Schirawski J Mendoza-Mendoza A Greilinger D Münch K Rössel N Scherer M Vranes M Ladendorf O Vincon V Fuchs U Sandrock B Meng S Ho EC Cahill MJ Boyce KJ Klose J 《Nature》2006,444(7115):97-101
Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens. 相似文献
34.
The mitochondrial deoxyribonucleotide (dNTP) pool is separated from the cytosolic pool because the mitochondria inner membrane is impermeable to charged molecules. The mitochondrial pool is maintained by either import of cytosolic dNTPs through dedicated transporters or by salvaging deoxynucleosides within the mitochondria; apparently, enzymes of the de novo dNTP synthesis pathway are not present in the mitochondria. In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis depends solely on the mitochondrial salvage pathway enzymes, the deoxyribonucleosides kinases. Two of the four human deoxyribonucleoside kinases, deoxyguanosine kinase (dGK) and thymidine kinase-2 (TK2), are expressed in mitochondria. Human dGK efficiently phosphorylates deoxyguanosine and deoxyadenosine, whereas TK2 phosphorylates deoxythymidine, deoxycytidine and deoxyuridine. Here we identify two mutations in TK2, histidine 90 to asparagine and isoleucine 181 to asparagine, in four individuals who developed devastating myopathy and depletion of muscular mitochondrial DNA in infancy. In these individuals, the activity of TK2 in muscle mitochondria is reduced to 14-45% of the mean value in healthy control individuals. Mutations in TK2 represent a new etiology for mitochondrial DNA depletion, underscoring the importance of the mitochondrial dNTP pool in the pathogenesis of mitochondrial depletion. 相似文献
35.
Gissen P Johnson CA Morgan NV Stapelbroek JM Forshew T Cooper WN McKiernan PJ Klomp LW Morris AA Wraith JE McClean P Lynch SA Thompson RJ Lo B Quarrell OW Di Rocco M Trembath RC Mandel H Wali S Karet FE Knisely AS Houwen RH Kelly DA Maher ER 《Nature genetics》2004,36(4):400-404
ARC syndrome (OMIM 208085) is an autosomal recessive multisystem disorder characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase (gGT) activity. Platelet dysfunction is common. Affected infants do not thrive and usually die in the first year of life. To elucidate the molecular basis of ARC, we mapped the disease to a 7-cM interval on 15q26.1 and then identified germline mutations in the gene VPS33B in 14 kindreds with ARC. VPS33B encodes a homolog of the class C yeast vacuolar protein sorting gene, Vps33, that contains a Sec1-like domain important in the regulation of vesicle-to-target SNARE complex formation and subsequent membrane fusion. 相似文献
36.
Paredes B Widera A Murg V Mandel O Fölling S Cirac I Shlyapnikov GV Hänsch TW Bloch I 《Nature》2004,429(6989):277-281
Strongly correlated quantum systems are among the most intriguing and fundamental systems in physics. One such example is the Tonks-Girardeau gas, proposed about 40 years ago, but until now lacking experimental realization; in such a gas, the repulsive interactions between bosonic particles confined to one dimension dominate the physics of the system. In order to minimize their mutual repulsion, the bosons are prevented from occupying the same position in space. This mimics the Pauli exclusion principle for fermions, causing the bosonic particles to exhibit fermionic properties. However, such bosons do not exhibit completely ideal fermionic (or bosonic) quantum behaviour; for example, this is reflected in their characteristic momentum distribution. Here we report the preparation of a Tonks-Girardeau gas of ultracold rubidium atoms held in a two-dimensional optical lattice formed by two orthogonal standing waves. The addition of a third, shallower lattice potential along the long axis of the quantum gases allows us to enter the Tonks-Girardeau regime by increasing the atoms' effective mass and thereby enhancing the role of interactions. We make a theoretical prediction of the momentum distribution based on an approach in which trapped bosons acquire fermionic properties, finding that it agrees closely with the measured distribution. 相似文献
37.
Architecture and material properties of diatom shells provide effective mechanical protection 总被引:10,自引:0,他引:10
Diatoms are the major contributors to phytoplankton blooms in lakes and in the sea and hence are central in aquatic ecosystems and the global carbon cycle. All free-living diatoms differ from other phytoplankton groups in having silicified cell walls in the form of two 'shells' (the frustule) of manifold shape and intricate architecture whose function and role, if any, in contributing to the evolutionary success of diatoms is under debate. We explored the defence potential of the frustules as armour against predators by measuring their strength. Real and virtual loading tests (using calibrated glass microneedles and finite element analysis) were performed on centric and pennate diatom cells. Here we show that the frustules are remarkably strong by virtue of their architecture and the material properties of the diatom silica. We conclude that diatom frustules have evolved as mechanical protection for the cells because exceptional force is required to break them. The evolutionary arms race between diatoms and their specialized predators will have had considerable influence in structuring pelagic food webs and biogeochemical cycles. 相似文献
38.
Mlle M. Jacob Mme L. Mandel P. Mandel 《Cellular and molecular life sciences : CMLS》1954,10(5):218-220
Summary The quantitative study of whole liver DNA and liver nuclei DNA at various ages, and the simultaneous study of oxygen uptake shows the following facts:(1) The rate of oxygen consumption to the fresh weight or to the DNA or to diploid chromosomes group is the same for the adult or the young aged 8 days. The values of oxygen consumption calculated for one cell or for one nucleus (taking notice of the fact that the mean level of liver nuclei DNA varies with the age) at 8 days is only the half of the adult value. Even at two months the value is 20% lower than in the adult.(2) In older animals there is a decrease of oxygen uptake which is more noticeable on a cellular scale than with the classical rate to fresh or dry weight. We affirm the fact that the diminution of the oxygen uptake of each cell is compensated by the increase of the number of cells. 相似文献
39.
In a pioneering experiment, Hanbury Brown and Twiss (HBT) demonstrated that noise correlations could be used to probe the properties of a (bosonic) particle source through quantum statistics; the effect relies on quantum interference between possible detection paths for two indistinguishable particles. HBT correlations--together with their fermionic counterparts--find numerous applications, ranging from quantum optics to nuclear and elementary particle physics. Spatial HBT interferometry has been suggested as a means to probe hidden order in strongly correlated phases of ultracold atoms. Here we report such a measurement on the Mott insulator phase of a rubidium Bose gas as it is released from an optical lattice trap. We show that strong periodic quantum correlations exist between density fluctuations in the expanding atom cloud. These spatial correlations reflect the underlying ordering in the lattice, and find a natural interpretation in terms of a multiple-wave HBT interference effect. The method should provide a useful tool for identifying complex quantum phases of ultracold bosonic and fermionic atoms. 相似文献
40.