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排序方式: 共有232条查询结果,搜索用时 15 毫秒
191.
Bicknell LS Bongers EM Leitch A Brown S Schoots J Harley ME Aftimos S Al-Aama JY Bober M Brown PA van Bokhoven H Dean J Edrees AY Feingold M Fryer A Hoefsloot LH Kau N Knoers NV Mackenzie J Opitz JM Sarda P Ross A Temple IK Toutain A Wise CA Wright M Jackson AP 《Nature genetics》2011,43(4):356-359
Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears1?3. Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evident, intellect is usually normal in this syndrome. We report here that individuals with this disorder show marked locus heterogeneity, and we identify mutations in five separate genes: ORC1, ORC4, ORC6, CDT1 and CDC6. All of these genes encode components of the pre-replication complex, implicating defects in replication licensing as the cause of a genetic syndrome with distinct developmental abnormalities. 相似文献
192.
Philip Hans Franses 《Journal of forecasting》1996,15(2):83-95
A periodically integrated (PI) time series process assumes that the stochastic trend can be removed using a seasonally varying differencing filter. In this paper the multi-step forecast error variances are derived for a quarterly PI time series when low-order periodic autoregressions adequately describe the data. The forecast error variances display seasonal variation, indicating that observations in some seasons can be forecast more precise than those in others. Two examples illustrate the empirical relevance of calculating forecast error variances. A by-product of the analysis is an expression for the seasonally varying impact of the stochastic trend. 相似文献
193.
Dekki N Refai E Holmberg R Köhler M Jörnvall H Berggren PO Juntti-Berggren L 《Cellular and molecular life sciences : CMLS》2012,69(10):1733-1743
Transthyretin (TTR) is a functional protein in the pancreatic β-cell. It promotes insulin release and protects against β-cell
death. We now demonstrate by ligand blotting, adsorption to specific magnetic beads, and surface plasmon resonance that TTR
binds to glucose-regulated proteins (Grps)78, 94, and 170, which are members of the endoplasmic reticulum chaperone family,
but Grps78 and 94 have also been found at the plasma membrane. The effect of TTR on changes in cytoplasmic free Ca2+ concentration ([Ca2+]i) was abolished if the cells were treated with either dynasore, a specific inhibitor of dynamin GTPase that blocks clathrin-mediated
endocytosis, or an antibody against Grp78, that prevents TTR from binding to Grp78. The conclusion is that TTR binds to Grp78
at the plasma membrane, is internalized into the β-cell via a clathrin-dependent pathway, and that this internalization is
necessary for the effects of TTR on β-cell function. 相似文献
194.
Hyun Woo Choi Jong Soo Kim Hyo Jin Jang Sol Choi Jae-Hwan Kim Hans R. Sch?ler Jeong Tae Do 《Cellular and molecular life sciences : CMLS》2012,69(23):4067-4077
The restricted gene expression pattern of a differentiated cell can be reversed by fusion of the somatic cell with a more developmentally potent cell type, such as an embryonic stem (ES) cell. During this reprogramming process, somatic cells obtain most of the characteristics of pluripotent cells. Reactivation of an inactive X chromosome (Xi) is an important epigenetic marker confirming the pluripotent reprogramming of somatic cells. Female somatic cells contain one active X chromosome (Xa) and one Xi, and following the fusion of these cells with male ES cells, the Xi becomes activated, resulting in XaXaXaY fusion hybrid cells. To monitor Xi reactivation, transgenic female neural stem cells (fNSCs) carrying a green fluorescent protein (GFP) reporter gene expressed on the Xa (X-GFP), but not on the Xi, were used for reprogramming. XaXiGFP NSCs, whose GFP reporter was silenced, were fused with HM1 ES cells (XY) to induce pluripotent reprogramming. The XiGFP of NSCs were found to be activated on day 4 post-fusion, indicating reactivation of the Xi. Hybrid cells showed pluripotent cell-specific characteristics cells including inactivation of the NSC marker Nestin, DNA demethylation of Oct4, DNA methylation of Nestin, and reactivation of the Xi. Following differentiation of the (GFP-positive) hybrid cells through embryoid body formation, the proportion of GFP-negative cells was found to be approximately 26?%, indicating that there was random inactivation of one of the three Xas. Here, we showed that the Xi of somatic cells is reprogrammed to the Xa state and that cellular differentiation occurs randomly, i.e., regardless of the Xa or Xi state, indicating that the memory of the Xi of somatic cells has been erased and reset to the ground state (i.e., inner cell mass-like state), indicating that random X-chromosome inactivation occurs upon differentiation. 相似文献
195.
Wortmann SB Vaz FM Gardeitchik T Vissers LE Renkema GH Schuurs-Hoeijmakers JH Kulik W Lammens M Christin C Kluijtmans LA Rodenburg RJ Nijtmans LG Grünewald A Klein C Gerhold JM Kozicz T van Hasselt PM Harakalova M Kloosterman W Barić I Pronicka E Ucar SK Naess K Singhal KK Krumina Z Gilissen C van Bokhoven H Veltman JA Smeitink JA Lefeber DJ Spelbrink JN Wevers RA Morava E de Brouwer AP 《Nature genetics》2012,44(7):797-802
Using exome sequencing, we identify SERAC1 mutations as the cause of MEGDEL syndrome, a recessive disorder of dystonia and deafness with Leigh-like syndrome, impaired oxidative phosphorylation and 3-methylglutaconic aciduria. We localized SERAC1 at the interface between the mitochondria and the endoplasmic reticulum in the mitochondria-associated membrane fraction that is essential for phospholipid exchange. A phospholipid analysis in patient fibroblasts showed elevated concentrations of phosphatidylglycerol-34:1 (where the species nomenclature denotes the number of carbon atoms in the two acyl chains:number of double bonds in the two acyl groups) and decreased concentrations of phosphatidylglycerol-36:1 species, resulting in an altered cardiolipin subspecies composition. We also detected low concentrations of bis(monoacyl-glycerol)-phosphate, leading to the accumulation of free cholesterol, as shown by abnormal filipin staining. Complementation of patient fibroblasts with wild-type human SERAC1 by lentiviral infection led to a decrease and partial normalization of the mean ratio of phosphatidylglycerol-34:1 to phosphatidylglycerol-36:1. Our data identify SERAC1 as a key player in the phosphatidylglycerol remodeling that is essential for both mitochondrial function and intracellular cholesterol trafficking. 相似文献
196.
Hinkes B Wiggins RC Gbadegesin R Vlangos CN Seelow D Nürnberg G Garg P Verma R Chaib H Hoskins BE Ashraf S Becker C Hennies HC Goyal M Wharram BL Schachter AD Mudumana S Drummond I Kerjaschki D Waldherr R Dietrich A Ozaltin F Bakkaloglu A Cleper R Basel-Vanagaite L Pohl M Griebel M Tsygin AN Soylu A Müller D Sorli CS Bunney TD Katan M Liu J Attanasio M O'toole JF Hasselbacher K Mucha B Otto EA Airik R Kispert A Kelley GG Smrcka AV Gudermann T Holzman LB Nürnberg P Hildebrandt F 《Nature genetics》2006,38(12):1397-1405
Nephrotic syndrome, a malfunction of the kidney glomerular filter, leads to proteinuria, edema and, in steroid-resistant nephrotic syndrome, end-stage kidney disease. Using positional cloning, we identified mutations in the phospholipase C epsilon gene (PLCE1) as causing early-onset nephrotic syndrome with end-stage kidney disease. Kidney histology of affected individuals showed diffuse mesangial sclerosis (DMS). Using immunofluorescence, we found PLCepsilon1 expression in developing and mature glomerular podocytes and showed that DMS represents an arrest of normal glomerular development. We identified IQ motif-containing GTPase-activating protein 1 as a new interaction partner of PLCepsilon1. Two siblings with a missense mutation in an exon encoding the PLCepsilon1 catalytic domain showed histology characteristic of focal segmental glomerulosclerosis. Notably, two other affected individuals responded to therapy, making this the first report of a molecular cause of nephrotic syndrome that may resolve after therapy. These findings, together with the zebrafish model of human nephrotic syndrome generated by plce1 knockdown, open new inroads into pathophysiology and treatment mechanisms of nephrotic syndrome. 相似文献
197.
198.
Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers 总被引:21,自引:0,他引:21
199.
We analyze the behavior of experts who quote forecasts for monthly SKU‐level sales data, where we compare data before and after the moment that experts received different kinds of feedback on their behavior. We have data for 21 experts located in as many countries who make SKU‐level forecasts for a variety of pharmaceutical products for October 2006 to September 2007. We study the behavior of the experts by comparing their forecasts with those from an automated statistical program, and we report the forecast accuracy over these 12 months. In September 2007 these experts were given feedback on their behavior and they received training at the headquarters office, where specific attention was given to the ins and outs of the statistical program. Next, we study the behavior of the experts for the 3 months after the training session, i.e. October 2007 to December 2007. Our main conclusion is that in the second period the experts’ forecasts deviated less from the statistical forecasts and that their accuracy improved substantially. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
200.
Hans C. Ohanian 《Studies in History and Philosophy of Science Part B: Studies in History and Philosophy of Modern Physics》2012,43(3):215-217
N. D. Mermin has proposed an “elaboration” of Einstein's 1905 derivation that supposedly fixes the flaws that I identified in this derivation. By specific examples taken from Einstein's own later work, I show that Mermin's elaboration is fraught with misconceptions. 相似文献