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11.
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis 总被引:21,自引:0,他引:21
Palmer CN Irvine AD Terron-Kwiatkowski A Zhao Y Liao H Lee SP Goudie DR Sandilands A Campbell LE Smith FJ O'Regan GM Watson RM Cecil JE Bale SJ Compton JG DiGiovanna JJ Fleckman P Lewis-Jones S Arseculeratne G Sergeant A Munro CS El Houate B McElreavey K Halkjaer LB Bisgaard H Mukhopadhyay S McLean WH 《Nature genetics》2006,38(4):441-446
Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease. 相似文献
12.
Named as new is Sclerocactus schlesseri Heil & Welsh. The taxon is described and its relationships discussed. 相似文献
13.
Mao JH Perez-Losada J Wu D Delrosario R Tsunematsu R Nakayama KI Brown K Bryson S Balmain A 《Nature》2004,432(7018):775-779
The FBXW7/hCDC4 gene encodes a ubiquitin ligase implicated in the control of chromosome stability. Here we identify the mouse Fbxw7 gene as a p53-dependent tumour suppressor gene by using a mammalian genetic screen for p53-dependent genes involved in tumorigenesis. Radiation-induced lymphomas from p53+/- mice, but not those from p53-/- mice, show frequent loss of heterozygosity and a 10% mutation rate of the Fbxw7 gene. Fbxw7+/- mice have greater susceptibility to radiation-induced tumorigenesis, but most tumours retain and express the wild-type allele, indicating that Fbxw7 is a haploinsufficient tumour suppressor gene. Loss of Fbxw7 alters the spectrum of tumours that develop in p53 deficient mice to include a range of tumours in epithelial tissues such as the lung, liver and ovary. Mouse embryo fibroblasts from Fbxw7-deficient mice, or wild-type mouse cells expressing Fbxw7 small interfering RNA, have higher levels of Aurora-A kinase, c-Jun and Notch4, but not of cyclin E. We propose that p53-dependent loss of Fbxw7 leads to genetic instability by mechanisms that might involve the activation of Aurora-A, providing a rationale for the early occurrence of these mutations in human cancers. 相似文献
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Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor 总被引:72,自引:0,他引:72
Ohtaki T Shintani Y Honda S Matsumoto H Hori A Kanehashi K Terao Y Kumano S Takatsu Y Masuda Y Ishibashi Y Watanabe T Asada M Yamada T Suenaga M Kitada C Usuki S Kurokawa T Onda H Nishimura O Fujino M 《Nature》2001,411(6837):613-617
Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach. 相似文献
16.
为了实现稳定跳跃步态,单足机器人需要持续补充能量以克服阻尼、碰撞等造成的能耗。该文针对腿部有阻尼的单足机器人,分析不同补能方式和补能时机对单足机器人竖直跳跃阻尼能耗的影响。理论分析和仿真实验结果表明:在支撑相单足机器人躯干上升阶段补能具有更高的补能效率,且补能起始位置越高、距起跳点越近,补能效率越高;在支撑相单足机器人躯干下降阶段补能会影响地面对足端的支持力,导致机器人站立不稳;如果在上升阶段补能,补能起始位置越高,补充相同能量时对驱动器峰值驱动力及峰值驱动功率要求越高。该研究结果为跳跃补能策略选择以及设计高效跳跃机器人控制器提供了参考。 相似文献
17.
The hydrological simulation program FORTRAN (HSPF) is a comprehensive watershed model designed to simulate water quantity and quality processes.It is used widely throughout the world.Calculating discharge from a stream reach by HSPF is based mainly on function tables (FTABLEs),which describe the relationship between surface area,stream stage,volume,and discharge.The traditional method of FTABLE generation (using general stream cross-sections and the Manning equation or other discharge relationships) can be time-consuming and inaccurate when there are limited calibration stations and survey data.Recent insights into generalized coupled stage/storage and stage/discharge relationships,however,offer the potential to improve both the speed and accuracy of compiling FTABLEs and thus HSPF models.This study tested the application of these insights in generating FTABLEs.The study domain included 18 gauging stations in a coastal plain environment on the Peace River watershed in West-Central Florida.In the calibration of this model,wetlands were treated as reaches in HSPF with storage-attenuation characteristics.Over the simulation period,the modeled daily flow and stage correlated well with observed data at all ganging stations along the Peace River.The Nash-Sutcliffe efficiency and correlation coefficient computed using observed and simulated daily flows were 0.90 and 0.91,respectively,at the Peace River outlet.Rigorous testing found that the new system for calibrating the FTABLEs improved the model predictive ability and efficiency.Uncertainty in un-calibrated station performance was also reduced.The model parameters obtained in this study could potentially serve as reference values for model application in similar climatic regions.They may also have particular relevance in disaster management,as the simulation period extended over the hurricane season of 2004,and the model domain was within a high hurricane impact zone.The possible effects of hurricanes on discharge are also briefly discussed. 相似文献
18.
The purpose of this research is to propose an early restoration for lifeline systems after earthquake disasters. The previous researches show that the optimization of the restoration schedule by using genetic algorithm (GA) is powerful. However, those are not considering the uncertain environment after earthquake disasters. The circumstances of the damage at devastated areas are very changeable due to the aftershock, fire disaster and bad weather. In addition, the restoring works may delay by unexpected accidents. Therefore, it is necessary to obtain the restoration schedule which has robustness, because the actual restoring works could not progress smoothly under the uncertain environment. GA considering uncertainty (GACU) can treat various uncertainties involved, but it is difficult to obtain the robust schedule. In this study, an attempt is made to develop a decision support system of the optimal restoration scheduling by using the improved GACU. 相似文献
19.
T. Saito Y. Shibata T. Kurokawa N. Ishida 《Cellular and molecular life sciences : CMLS》1979,35(5):685-686
Summary The inhibitory effect of various purine derivatives on PHA-induced human lymphocyte blast formation was studied. Two nucleoside cytokinins, N6-benzyladenosine and N6-isopentenyladenosine, inhibited blast formation at concentrations as low as 10–6 M. However, the other cytokinins, which lacked the ribosyl residue at N9 position, had to be at the higher molar concentration of 10–4 before they could induce the same inhibitory effect. 相似文献
20.