首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   730篇
  免费   14篇
  国内免费   2篇
系统科学   16篇
理论与方法论   26篇
现状及发展   446篇
研究方法   38篇
综合类   194篇
自然研究   26篇
  2018年   16篇
  2017年   15篇
  2016年   14篇
  2015年   11篇
  2014年   18篇
  2013年   13篇
  2012年   22篇
  2011年   45篇
  2010年   20篇
  2009年   7篇
  2008年   27篇
  2007年   15篇
  2006年   20篇
  2005年   30篇
  2004年   16篇
  2003年   23篇
  2002年   17篇
  2001年   18篇
  2000年   11篇
  1999年   11篇
  1998年   9篇
  1993年   5篇
  1991年   10篇
  1990年   7篇
  1989年   8篇
  1985年   8篇
  1984年   9篇
  1983年   5篇
  1982年   8篇
  1981年   16篇
  1980年   9篇
  1979年   21篇
  1978年   20篇
  1977年   9篇
  1976年   20篇
  1975年   9篇
  1974年   10篇
  1973年   14篇
  1972年   8篇
  1971年   17篇
  1970年   10篇
  1969年   12篇
  1968年   20篇
  1967年   11篇
  1966年   9篇
  1965年   18篇
  1964年   6篇
  1954年   5篇
  1948年   6篇
  1947年   6篇
排序方式: 共有746条查询结果,搜索用时 15 毫秒
591.
We investigate the forecasting ability of the most commonly used benchmarks in financial economics. We approach the usual caveats of probabilistic forecasts studies—small samples, limited models, and nonholistic validations—by performing a comprehensive comparison of 15 predictive schemes during a time period of over 21 years. All densities are evaluated in terms of their statistical consistency, local accuracy and forecasting errors. Using a new composite indicator, the integrated forecast score, we show that risk‐neutral densities outperform historical‐based predictions in terms of information content. We find that the variance gamma model generates the highest out‐of‐sample likelihood of observed prices and the lowest predictive errors, whereas the GARCH‐based GJR‐FHS delivers the most consistent forecasts across the entire density range. In contrast, lognormal densities, the Heston model, or the nonparametric Breeden–Litzenberger formula yield biased predictions and are rejected in statistical tests.  相似文献   
592.

Aims

G-protein coupled receptor 56 (GPR56) is the most abundant islet-expressed G-protein coupled receptor, suggesting a potential role in islet function. This study evaluated islet expression of GPR56 and its endogenous ligand collagen III, and their effects on β-cell function.

Methods

GPR56 and collagen III expression in mouse and human pancreas sections was determined by fluorescence immunohistochemistry. Effects of collagen III on β-cell proliferation, apoptosis, intracellular calcium ([Ca2+]i) and insulin secretion were determined by cellular BrdU incorporation, caspase 3/7 activities, microfluorimetry and radioimmunoassay, respectively. The role of GPR56 in islet vascularisation and innervation was evaluated by immunohistochemical staining for CD31 and TUJ1, respectively, in pancreases from wildtype (WT) and Gpr56?/? mice, and the requirement of GPR56 for normal glucose homeostasis was determined by glucose tolerance tests in WT and Gpr56?/? mice.

Results

Immunostaining of mouse and human pancreases revealed that GPR56 was expressed by islet β-cells while collagen III was confined to the peri-islet basement membrane and islet capillaries. Collagen III protected β-cells from cytokine-induced apoptosis, triggered increases in [Ca2+]i and potentiated glucose-induced insulin secretion from WT islets but not from Gpr56?/? islets. Deletion of GPR56 did not affect glucose-induced insulin secretion in vitro and it did not impair glucose tolerance in adult mice. GPR56 was not required for normal islet vascularisation or innervation.

Conclusion

We have demonstrated that collagen III improves islet function by increasing insulin secretion and protecting against apoptosis. Our data suggest that collagen III may be effective in optimising islet function to improve islet transplantation outcomes, and GPR56 may be a target for the treatment of type 2 diabetes.
  相似文献   
593.
Our understanding of flippase-mediated lipid translocation and membrane vesiculation, and the involvement of P-type ATPases in these processes is just beginning to emerge. The results obtained so far demonstrate significant complexity within this field and point to major tasks for future research. Most importantly, biochemical characterization of P4-ATPases is required in order to clarify whether these transporters indeed are capable of catalyzing transmembrane phospholipid flipping. The β-subunit of P4-ATPases shows unexpected similarities between the β- and γ-subunits of the Na+/K+-ATPase. It is likely that these proteins provide a similar solution to similar problems, and might have adopted similar structures to accomplish these tasks. No P4-ATPases have been identified in the endoplasmic reticulum and it remains an intriguing possibility that, in this compartment, P5A-ATPases are functional homologues of P4-ATPases. Received 19 June 2008; received after revision 31 July 2008; accepted 15 August 2008  相似文献   
594.
595.
Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.  相似文献   
596.
We identified and replicated an association between ITGAM (CD11b) at 16p11.2 and risk of systemic lupus erythematosus (SLE) in 3,818 individuals of European descent. The strongest association was at a nonsynonymous SNP, rs1143679 (P = 1.7 x 10(-17), odds ratio = 1.78). We further replicated this association in two independent samples of individuals of African descent (P = 0.0002 and 0.003; overall meta-analysis P = 6.9 x 10(-22)). The genetic association between ITGAM and SLE implicates the alpha(M)beta2-integrin adhesion pathway in disease development.  相似文献   
597.
Accretion of gas onto black holes is thought to power the relativistic jets of material ejected from active galactic nuclei (AGN) and the 'microquasars' located in our Galaxy. In microquasars, superluminal radio-emitting features appear and propagate along the jet shortly after sudden decreases in the X-ray fluxes. This establishes a direct observational link between the black hole and the jet: the X-ray dip is probably caused by the disappearance of a section of the inner accretion disk as it falls past the event horizon, while the remainder of the disk section is ejected into the jet, creating the appearance of a superluminal bright spot. No such connection has hitherto been established for AGN, because of insufficient multi-frequency data. Here we report the results of three years of monitoring the X-ray and radio emission of the galaxy 3C120. As has been observed for microquasars, we find that dips in the X-ray emission are followed by ejections of bright superluminal knots in the radio jet. The mean time between X-ray dips appears to scale roughly with the mass of the black hole, although there are at present only a few data points.  相似文献   
598.
Physical laws are believed to be invariant under the combined transformations of charge, parity and time reversal (CPT symmetry). This implies that an antimatter particle has exactly the same mass and absolute value of charge as its particle counterpart. Metastable antiprotonic helium (pHe(+)) is a three-body atom consisting of a normal helium nucleus, an electron in its ground state and an antiproton (p) occupying a Rydberg state with high principal and angular momentum quantum numbers, respectively n and l, such that n?≈?l?+?1?≈?38. These atoms are amenable to precision laser spectroscopy, the results of which can in principle be used to determine the antiproton-to-electron mass ratio and to constrain the equality between the antiproton and proton charges and masses. Here we report two-photon spectroscopy of antiprotonic helium, in which p(3)He(+) and p(4)He(+) isotopes are irradiated by two counter-propagating laser beams. This excites nonlinear, two-photon transitions of the antiproton of the type (n, l)?→?(n?-?2, l?-?2) at deep-ultraviolet wavelengths (λ = 139.8, 193.0 and 197.0?nm), which partly cancel the Doppler broadening of the laser resonance caused by the thermal motion of the atoms. The resulting narrow spectral lines allowed us to measure three transition frequencies with fractional precisions of 2.3-5 parts in 10(9). By comparing the results with three-body quantum electrodynamics calculations, we derived an antiproton-to-electron mass ratio of 1,836.1526736(23), where the parenthetical error represents one standard deviation. This agrees with the proton-to-electron value known to a similar precision.  相似文献   
599.
The aim of this study was to synthesize and characterize Fe_(x-1)S 2D-nanostructures with pyrrhotite phase,as well as to explore their biological(antibacterial and cytotoxic)properties,namely the expression of reactive oxygen species(ROS)in the exposure of cells and bacteria.Based on hydrothermal synthesis,the characterization of asprepared 2D-nanostructures was performed by XRD,SEM,EDS,and TEM,in which the single-crystalline pyrrhotite phased Fe_(x-1)S nanoplate morphology was observed.The antibacterial activities of Fe_(x-1)S nanoplates against human pathogenic strains such as Staphylococcus aureus,Escherichia coli,and Enterococcus faecalis were tested.Minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)were determined following the broth microdilution method.Cytotoxicity and expression of intracellular ROS of pyrrhotite nanoplates on Human Gingival Fibroblast(HGF),Human Pulp Cells(HPC)and Human Osteoblast(HBC)were calculated.Cell viability was determined by the MTT method.All experiments were performed of three independent experiments and data were analyzed by Kruskal-Wallis and Mann-Whitney tests,also Pearson′s Correlation was performed.The nanoplates exhibited good bactericidal effect.All types of cells tested showed slight cytotoxicity.It was found that intracellular ROS is produced when cells and bacteria tested are exposed to pyrrhotite nanoplates in presence of both air and peroxide hydrogen.ROS production levels were higher in the bacteria than the cells exposed to these nanoplates.  相似文献   
600.
Methane formation from long-chain alkanes by anaerobic microorganisms.   总被引:20,自引:0,他引:20  
Biological formation of methane is the terminal process of biomass degradation in aquatic habitats where oxygen, nitrate, ferric iron and sulphate have been depleted as electron acceptors. The pathway leading from dead biomass to methane through the metabolism of anaerobic bacteria and archaea is well understood for easily degradable biomolecules such as carbohydrates, proteins and lipids. However, little is known about the organic compounds that lead to methane in old anoxic sediments where easily degradable biomolecules are no longer available. One class of naturally formed long-lived compounds in such sediments is the saturated hydrocarbons (alkanes). Alkanes are usually considered to be inert in the absence of oxygen, nitrate or sulphate, and the analysis of alkane patterns is often used for biogeochemical characterization of sediments. However, alkanes might be consumed in anoxic sediments below the zone of sulphate reduction, but the underlying process has not been elucidated. Here we used enrichment cultures to show that the biological conversion of long-chain alkanes to the simplest hydrocarbon, methane, is possible under strictly anoxic conditions.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号