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排序方式: 共有87条查询结果,搜索用时 31 毫秒
51.
TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome 总被引:1,自引:0,他引:1
C Boileau DC Guo N Hanna ES Regalado D Detaint L Gong M Varret SK Prakash AH Li H d'Indy AC Braverman B Grandchamp CS Kwartler L Gouya RL Santos-Cortez M Abifadel SM Leal C Muti J Shendure MS Gross MJ Rieder A Vahanian DA Nickerson JB Michel;National Heart Lung Blood Institute 《Nature genetics》2012,44(8):916-921
A predisposition for thoracic aortic aneurysms leading to acute aortic dissections can be inherited in families in an autosomal dominant manner. Genome-wide linkage analysis of two large unrelated families with thoracic aortic disease followed by whole-exome sequencing of affected relatives identified causative mutations in TGFB2. These mutations-a frameshift mutation in exon 6 and a nonsense mutation in exon 4-segregated with disease with a combined logarithm of odds (LOD) score of 7.7. Sanger sequencing of 276 probands from families with inherited thoracic aortic disease identified 2 additional TGFB2 mutations. TGFB2 encodes transforming growth factor (TGF)-β2, and the mutations are predicted to cause haploinsufficiency for TGFB2; however, aortic tissue from cases paradoxically shows increased TGF-β2 expression and immunostaining. Thus, haploinsufficiency for TGFB2 predisposes to thoracic aortic disease, suggesting that the initial pathway driving disease is decreased cellular TGF-β2 levels leading to a secondary increase in TGF-β2 production in the diseased aorta. 相似文献
52.
Stephane R. Gross Connie Goh Then Sin Roger Barraclough Philip S. Rudland 《Cellular and molecular life sciences : CMLS》2014,71(9):1551-1579
The vast diversity of S100 proteins has demonstrated a multitude of biological correlations with cell growth, cell differentiation and cell survival in numerous physiological and pathological conditions in all cells of the body. This review summarises some of the reported regulatory functions of S100 proteins (namely S100A1, S100A2, S100A4, S100A6, S100A7, S100A8/S100A9, S100A10, S100A11, S100A12, S100B and S100P) on cellular migration and invasion, established in both culture and animal model systems and the possible mechanisms that have been proposed to be responsible. These mechanisms involve intracellular events and components of the cytoskeletal organisation (actin/myosin filaments, intermediate filaments and microtubules) as well as extracellular signalling at different cell surface receptors (RAGE and integrins). Finally, we shall attempt to demonstrate how aberrant expression of the S100 proteins may lead to pathological events and human disorders and furthermore provide a rationale to possibly explain why the expression of some of the S100 proteins (mainly S100A4 and S100P) has led to conflicting results on motility, depending on the cells used. 相似文献
53.
Ari Gross 《Studies in History and Philosophy of Science Part B: Studies in History and Philosophy of Modern Physics》2012,43(3):184-194
This paper aims to give a substantive account of how Feynman used diagrams in the first lectures in which he explained his new approach to quantum electrodynamics. By critically examining unpublished lecture notes, Feynman's use and interpretation of both “Feynman diagrams” and other visual representations will be illuminated. This paper will discuss how the morphology of Feynman's early diagrams were determined by both highly contextual issues, which molded his images to local needs and particular physical characterizations, and an overarching common diagrammatic style, which facilitated Feynman's movement between different diagrams despite their divergent forms and significance. 相似文献
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This article contributes to the literature on business cycle forecasts and their impact on asset prices by investigating how the 15‐second Xetra DAX returns reflect the monthly announcements of the two best‐known business cycle forecasts for Germany, i.e., the Ifo Business Climate Index and the ZEW Indicator of Economic Sentiment. The analysis disentangles ‘good’ macroeconomics news from ‘bad’ news and, simultaneously, considers time intervals with and without confounding announcements from other sources. Releases from both institutes lead to an immediate response of returns occurring 15 seconds after the announcements, i.e. within the first possible time interval. Announcements of both institutes are also clearly and immediately reflected in the volatility, which remains at a significantly higher level for approximately 2 minutes. Findings can be used to improve high‐frequency forecasts in stock markets. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
57.
M Endres T Fukuhara D Pekker M Cheneau P Schauss C Gross E Demler S Kuhr I Bloch 《Nature》2012,487(7408):454-458
Spontaneous symmetry breaking plays a key role in our understanding of nature. In relativistic quantum field theory, a broken continuous symmetry leads to the emergence of two types of fundamental excitation: massless Nambu-Goldstone modes and a massive 'Higgs' amplitude mode. An excitation of Higgs type is of crucial importance in the standard model of elementary particle physics, and also appears as a fundamental collective mode in quantum many-body systems. Whether such a mode exists in low-dimensional systems as a resonance-like feature, or whether it becomes overdamped through coupling to Nambu-Goldstone modes, has been a subject of debate. Here we experimentally find and study a Higgs mode in a two-dimensional neutral superfluid close to a quantum phase transition to a Mott insulating phase. We unambiguously identify the mode by observing the expected reduction in frequency of the onset of spectral response when approaching the transition point. In this regime, our system is described by an effective relativistic field theory with a two-component quantum field, which constitutes a minimal model for spontaneous breaking of a continuous symmetry. Additionally, all microscopic parameters of our system are known from first principles and the resolution of our measurement allows us to detect excited states of the many-body system at the level of individual quasiparticles. This allows for an in-depth study of Higgs excitations that also addresses the consequences of the reduced dimensionality and confinement of the system. Our work constitutes a step towards exploring emergent relativistic models with ultracold atomic gases. 相似文献
58.
Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function 总被引:64,自引:0,他引:64
Parrish-Novak J Dillon SR Nelson A Hammond A Sprecher C Gross JA Johnston J Madden K Xu W West J Schrader S Burkhead S Heipel M Brandt C Kuijper JL Kramer J Conklin D Presnell SR Berry J Shiota F Bort S Hambly K Mudri S Clegg C Moore M Grant FJ Lofton-Day C Gilbert T Rayond F Ching A Yao L Smith D Webster P Whitmore T Maurer M Kaushansky K Holly RD Foster D 《Nature》2000,408(6808):57-63
Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3. 相似文献
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Cytoskeletal molecular motors belonging to the kinesin and dynein families transport cargos (for example, messenger RNA, endosomes, virus) on polymerized linear structures called microtubules in the cell. These 'nanomachines' use energy obtained from ATP hydrolysis to generate force, and move in a step-like manner on microtubules. Dynein has a complex and fundamentally different structure from other motor families. Thus, understanding dynein's force generation can yield new insight into the architecture and function of nanomachines. Here, we use an optical trap to quantify motion of polystyrene beads driven along microtubules by single cytoplasmic dynein motors. Under no load, dynein moves predominantly with a mixture of 24-nm and 32-nm steps. When moving against load applied by an optical trap, dynein can decrease step size to 8 nm and produce force up to 1.1 pN. This correlation between step size and force production is consistent with a molecular gear mechanism. The ability to take smaller but more powerful strokes under load--that is, to shift gears--depends on the availability of ATP. We propose a model whereby the gear is downshifted through load-induced binding of ATP at secondary sites in the dynein head. 相似文献