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排序方式: 共有298条查询结果,搜索用时 13 毫秒
91.
Bitoun M Maugenre S Jeannet PY Lacène E Ferrer X Laforêt P Martin JJ Laporte J Lochmüller H Beggs AH Fardeau M Eymard B Romero NB Guicheney P 《Nature genetics》2005,37(11):1207-1209
Autosomal dominant centronuclear myopathy is a rare congenital myopathy characterized by delayed motor milestones and muscular weakness. In 11 families affected by centronuclear myopathy, we identified recurrent and de novo missense mutations in the gene dynamin 2 (DNM2, 19p13.2), which encodes a protein involved in endocytosis and membrane trafficking, actin assembly and centrosome cohesion. The transfected mutants showed reduced labeling in the centrosome, suggesting that DNM2 mutations might cause centronuclear myopathy by interfering with centrosome function. 相似文献
92.
Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres 总被引:28,自引:0,他引:28
Telomeres allow cells to distinguish natural chromosome ends from damaged DNA and protect the ends from degradation and fusion. In human cells, telomere protection depends on the TTAGGG repeat binding factor, TRF2 (refs 1-4), which has been proposed to remodel telomeres into large duplex loops (t-loops). Here we show by nanoelectrospray tandem mass spectrometry that RAD50 protein is present in TRF2 immunocomplexes. Protein blotting showed that a small fraction of RAD50, MRE11 and the third component of the MRE11 double-strand break (DSB) repair complex, the Nijmegen breakage syndrome protein (NBS1), is associated with TRF2. Indirect immunofluorescence demonstrated the presence of RAD50 and MRE11 at interphase telomeres. NBS1 was associated with TRF2 and telomeres in S phase, but not in G1 or G2. Although the MRE11 complex accumulated in irradiation-induced foci (IRIFs) in response to gamma-irradiation, TRF2 did not relocate to IRIFs and irradiation did not affect the association of TRF2 with the MRE11 complex, arguing against a role for TRF2 in DSB repair. Instead, we propose that the MRE11 complex functions at telomeres, possibly by modulating t-loop formation. 相似文献
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Summary The selectivity of vitellogenin absorption by the locust oocyte was examined by comparing the uptake of vitellogenin and a haemolymph protein of similar molecular weight (MHP). Though both proteins occurred in the haemolymph at approximately the same concentration there occurred a 500-fold difference in accumulation of vitellogenin over MHP during a 24-h period. Surprisingly MHP did not accumulate in the oocyte during vitellogenesis. 相似文献
95.
A substantial percentage of human pregnancies are lost as spontaneous abortions after implantation. This is often caused by an inadequately developed placenta. Proper development of the placental vascular system is essential to nutrient and gas exchange between mother and developing embryo. Here we show that alpha(2)-adrenoceptors, which are activated by adrenaline and noradrenaline, are important regulators of placental structure and function. Mice with deletions in the genes encoding alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors died between embryonic days 9.5 and 11.5 from a severe defect in yolk-sac and placenta development. In wildtype placentae, alpha(2)-adrenoceptors are abundantly expressed in giant cells, which secrete angiogenic factors to initiate development of the placental vascular labyrinth. In placentae deficient in alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors, the density of fetal blood vessels in the labyrinth was markedly lower than normal, leading to death of the embryos as a result of reduced oxygen and nutrient supply. Basal phosphorylation of the extracellular signal regulated kinases ERK1 and ERK2 was also lower than normal, suggesting that activation of the mitogen-activated protein kinase (MAP kinase) pathway by alpha(2)-adrenoceptors is required for placenta and yolk-sac vascular development. Thus, alpha(2)-adrenoceptors are essential at the placental interface between mother and embryo to establish the circulatory system of the placenta and thus maintain pregnancy. 相似文献
96.
TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2 总被引:31,自引:0,他引:31
Pasparakis M Courtois G Hafner M Schmidt-Supprian M Nenci A Toksoy A Krampert M Goebeler M Gillitzer R Israel A Krieg T Rajewsky K Haase I 《Nature》2002,417(6891):861-866
The I kappa B kinase (IKK), consisting of the IKK1 and IKK2 catalytic subunits and the NEMO (also known as IKK gamma) regulatory subunit, phosphorylates I kappa B proteins, targeting them for degradation and thus inducing activation of NF-kappa B (reviewed in refs 1, 2). IKK2 and NEMO are necessary for NF-kappa B activation through pro-inflammatory signals. IKK1 seems to be dispensable for this function but controls epidermal differentiation independently of NF-kappa B. Previous studies suggested that NF-kappa B has a function in the growth regulation of epidermal keratinocytes. Mice lacking RelB or I kappa B alpha, as well as both mice and humans with heterozygous NEMO mutations, develop skin lesions. However, the function of NF-kappa B in the epidermis remains unclear. Here we used Cre/loxP-mediated gene targeting to investigate the function of IKK2 specifically in epidermal keratinocytes. IKK2 deficiency inhibits NF-kappa B activation, but does not lead to cell-autonomous hyperproliferation or impaired differentiation of keratinocytes. Mice with epidermis-specific deletion of IKK2 develop a severe inflammatory skin disease, which is caused by a tumour necrosis factor-mediated, alpha beta T-cell-independent inflammatory response that develops in the skin shortly after birth. Our results suggest that the critical function of IKK2-mediated NF-kappa B activity in epidermal keratinocytes is to regulate mechanisms that maintain the immune homeostasis of the skin. 相似文献
97.
Sahin E Colla S Liesa M Moslehi J Müller FL Guo M Cooper M Kotton D Fabian AJ Walkey C Maser RS Tonon G Foerster F Xiong R Wang YA Shukla SA Jaskelioff M Martin ES Heffernan TP Protopopov A Ivanova E Mahoney JE Kost-Alimova M Perry SR Bronson R Liao R Mulligan R Shirihai OS Chin L DePinho RA 《Nature》2011,470(7334):359-365
98.
Reconstruction of the geological history of Mars has been the focus of considerable attention over the past four decades, with important discoveries being made about variations in surface conditions. However, despite a significant increase in the amount of data related to the morphology, mineralogy and chemistry of the martian surface, there is no clear global picture of how magmatism has evolved over time and how these changes relate to the internal workings and thermal evolution of the planet. Here we present geochemical data derived from the Gamma Ray Spectrometer on board NASA's Mars Odyssey spacecraft, focusing on twelve major volcanic provinces of variable age. Our analysis reveals clear trends in composition that are found to be consistent with varying degrees of melting of the martian mantle. There is evidence for thickening of the lithosphere (17-25?km?Gyr(-1)) associated with a decrease in mantle potential temperature over time (30-40?K?Gyr(-1)). Our inferred thermal history of Mars, unlike that of the Earth, is consistent with simple models of mantle convection. 相似文献
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100.