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   7214篇
  免费   726篇
  国内免费   719篇
  8659篇
  2024年   24篇
  2023年   85篇
  2022年   228篇
  2021年   349篇
  2020年   249篇
  2019年   289篇
  2018年   289篇
  2017年   239篇
  2016年   295篇
  2015年   444篇
  2014年   543篇
  2013年   579篇
  2012年   638篇
  2011年   515篇
  2010年   330篇
  2009年   302篇
  2008年   372篇
  2007年   333篇
  2006年   311篇
  2005年   265篇
  2004年   271篇
  2003年   217篇
  2002年   254篇
  2001年   192篇
  2000年   162篇
  1999年   138篇
  1998年   124篇
  1997年   94篇
  1996年   81篇
  1995年   74篇
  1994年   65篇
  1993年   50篇
  1992年   51篇
  1991年   40篇
  1990年   27篇
  1989年   20篇
  1988年   26篇
  1987年   22篇
  1986年   13篇
  1985年   13篇
  1984年   29篇
  1983年   7篇
  1982年   6篇
  1981年   3篇
  1980年   1篇
排序方式: 共有8659条查询结果,搜索用时 0 毫秒
981.
The study investigated the preparation and characterization of biochars from water hyacinth at 300°C to 700°C for cadmium (Cd) removal from aqueous solutions. The adsorption process was dominated by oxygen-containing functional groups with irregular surfaces via esterification reactions. Furthermore, the mineral components in the biochars also contributed to Cd absorption through precipitation. Parameters such as the effects of solution pH, contact time, and initial concentration were studied. The optimum pH value was observed at 5.0, in which nearly 90% of Cd was removed. The maximum Cd adsorption capacities based on the Langmuir isotherm were calculated at 49.837, 36.899, and 25.826 mg g−1. The adsorption processes of the biochars followed the pseudo-second-order kinetics, with the equilibrium achieved around 5 h. The biochar from E. crassipes is a promising adsorbent for the treatment of wastewater, which can in turn convert one environmental problem to a new cleaning Technology.  相似文献   
982.
In genetic association testing, failure to properly control for population structure can lead to severely inflated type 1 error and power loss. Meanwhile, adjustment for relevant covariates is often desirable and sometimes necessary to protect against spurious association and to improve power. Many recent methods to account for population structure and covariates are based on linear mixed models (LMMs), which are primarily designed for quantitative traits. For binary traits, however, LMM is a misspecified model and can lead to deteriorated performance. We propose CARAT, a binary-trait association testing approach based on a mixed-effects quasi-likelihood framework, which exploits the dichotomous nature of the trait and achieves computational efficiency through estimating equations. We show in simulation studies that CARAT consistently outperforms existing methods and maintains high power in a wide range of population structure settings and trait models. Furthermore, CARAT is based on a retrospective approach, which is robust to misspecification of the phenotype model. We apply our approach to a genome-wide analysis of Crohn disease, in which we replicate association with 17 previously identified regions. Moreover, our analysis on 5p13.1, an extensively reported region of association, shows evidence for the presence of multiple independent association signals in the region. This example shows how CARAT can leverage known disease risk factors to shed light on the genetic architecture of complex traits.  相似文献   
983.
Transferrin and transferrin receptor are two key proteins of iron metabolism that have been identified to be hypoxia-inducible genes. Divalent metal transporter 1 (DMT1) is also a key transporter of iron under physiological conditions. In addition, in the 5' regulatory region of human DMT1 (between -412 and -570), there are two motifs (CCAAAGTGCTGGG) that are similar to hypoxia-inducible factor-1 (HIF-1) binding sites. It was therefore speculated that DMT1 might also be a hypoxia-inducible gene. We investigated the effects of hypoxia and hypoxia/re-oxygenation on the expression of DMT1 and the content of HIF-1alpha in HepG2 cells. As we expected, a very similar tendency in the responses of the expression of HIF-1alpha, DMT1+IRE (iron response element) and DMT1-IRE proteins to chemical (CoCl(2)) or physical hypoxia was observed. A highly significant correlation was found between the expression of DMT1 proteins and the contents of HIF-1 in hypoxic cells. After the cells were exposed to hypoxia and subsequent normoxia, no HIF-1alpha could be detected and a significant decrease in DMT1+IRE expression (P<0.05), but not in DMT1-IRE protein (versus the hypoxia group), was observed. The findings implied that the HIF-1 pathway might have a role in the regulation of DMT1+IRE expression during hypoxia.  相似文献   
984.
Toh SY  Gong J  Du G  Li JZ  Yang S  Ye J  Yao H  Zhang Y  Xue B  Li Q  Yang H  Wen Z  Li P 《PloS one》2008,3(8):e2890
Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27(-/-) mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse strains. Furthermore, we isolated mouse embryonic fibroblasts (MEFs) from wildtype and Fsp27(-/-) mice, followed by their differentiation into adipocytes in vitro. We found that Fsp27 is expressed in both brown adipose tissue (BAT) and white adipose tissue (WAT) and its levels were significantly elevated in the WAT and liver of leptin-deficient ob/ob mice. Fsp27(-/-) mice had increased energy expenditure, lower levels of plasma triglycerides and free fatty acids. Furthermore, Fsp27(-/-)and Fsp27/lep double-deficient mice are resistant to diet-induced obesity and display increased insulin sensitivity. Moreover, white adipocytes in Fsp27(-/-) mice have reduced triglycerides accumulation and smaller lipid droplets, while levels of mitochondrial proteins, mitochondrial size and activity are dramatically increased. We further demonstrated that BAT-specific genes and key metabolic controlling factors such as FoxC2, PPAR and PGC1alpha were all markedly upregulated. In contrast, factors inhibiting BAT differentiation such as Rb, p107 and RIP140 were down-regulated in the WAT of Fsp27(-/-) mice. Remarkably, Fsp27(-/-) MEFs differentiated in vitro show many brown adipocyte characteristics in the presence of the thyroid hormone triiodothyronine (T3). Our data thus suggest that Fsp27 acts as a novel regulator in vivo to control WAT identity, mitochondrial activity and insulin sensitivity.  相似文献   
985.
986.
Focal adhesion kinase (FAK) is a non‐receptor protein tyrosine kinase that regulates cell adhesion, proliferation and differentiation. In the present study, a rat model of high fat diet‐induced hypercholesterolaemia was established to investigate the involvement of FAK in lipid disorder‐related kidney diseases. We showed focal fusion of podocyte foot process that occurred at as early as 4 weeks in rats consuming high fat diet, preceding the onset of proteinuria when aberrant phosphorylation of FAK was found. These abnormalities were ameliorated by dietary intervention of TAE226, a reported inhibitor of FAK. FAK is also an adaptor protein initiating cascades of intracellular signals including c‐Src, Rho GTPase and mitogen‐activated protein kinase (MAPK). P38 MAPK belongs to the latter and is centrally involved in kidney diseases. Our cell culture data revealed oxidized low‐density lipoprotein (ox‐LDL) triggered hyper‐phosphorylation of FAK and p38, ectopic expression of cellular markers (manifested as decreased WT1, podocin and NEPH1, and increased vimentin and mmp9), and re‐arrangement of F‐actin filaments with enhanced cell motility; these mutations were significantly rectified by FAK shRNA. Notably, pre‐treatment of p38 inhibitor did not alter FAK activation, albeit its deletion of p38 hyper‐activity and attenuation of cellular abnormalities, demonstrating that p38 acted as a downstream effector of FAK signalling and ox‐LDL damaged podocytes in a FAK/p38‐dependent manner. This was further identified by animal data that p38 activation was also abrogated by TAE226 treatment in hypercholesterolaemic rats, suggesting that FAK/p38 axis might also be involved in in vivo events. These findings provided a potential early mechanism of hypercholesterolaemia‐related podocyte damage and proteinuria.  相似文献   
987.
The chemical structure of conjugated polymers plays an important role in determining their physical properties that, in turn, dictates their performance in photovoltaic devices. 5‐Fluoro‐2,1,3‐benzothiadiazole, an asymmetric unit, is incorporated into a thiophene‐based polymer backbone to generate a hole conducting polymers with controlled regioregularity. A high dipole moment is seen in regioregular polymers, which have a tighter interchain stacking that promotes the formation of a morphology in bulk heterojunction blends with improved power conversion efficiencies. Aliphatic side chain substitution is systematically varied to understand the influence of side chain length and symmetry on the morphology and resultant performance. This side chain modification is found to influence crystal orientation and the phase separated morphology. Using the asymmetric side chain substitution with regioregularity of the main chain, an optimized power conversion efficiency of 9.06% is achieved, with an open circuit voltage of 0.72 V, a short circuit current of 19.63 mA cm?2, and a fill factor over 65%. These results demonstrate that the local chemical environment can dramatically influence the physical properties of the resultant material.  相似文献   
988.
Efficient ternary polymer solar cells are constructed by incorporating an electron‐deficient chromophore (5Z,5′Z)‐5,5′‐((7,7′‐(4,4,9,9‐tetrakis(4‐hexylphenyl)‐4,9‐dihydro‐s‐indaceno[1,2‐b:5,6‐b′]dithiophene‐2,7‐diyl)bis(6‐fluorobenzo[c][1,2,5]thiadiazole‐7,4‐diyl))bis(methanylylidene))bis(3‐ethyl‐2‐thioxothiazolidin‐4‐one) (IFBR) as an additional component into the bulk‐heterojunction film that consists of a wide‐bandgap conjugated benzodithiophene‐alt‐difluorobenzo[1,2,3]triazole based copolymer and a fullerene acceptor. With respect to the binary blend films, the incorporation of a certain amount of IFBR leads to simultaneously enhanced absorption coefficient, obviously extended absorption band, and improved open‐circuit voltage. Of particular interest is that devices based on ternary blend film exhibit much higher short‐circuit current densities than the binary counterparts, which can be attributed to the extended absorption profiles, enhanced absorption coefficient, favorable film morphology, as well as formation of cascade energy level alignment that is favorable for charge transfer. Further investigation indicates that the ternary blend device exhibits much shorter charge carrier extraction time, obviously reduced trap density and suppressed trap‐assisted recombination, which is favorable for achieving high short‐circuit current. The combination of these beneficial aspects leads to a significantly improved power conversion efficiency of 8.11% for the ternary device, which is much higher than those obtained from the binary counterparts. These findings demonstrate that IFBR can be a promising electron‐accepting material for the construction of ternary blend films toward high‐performance polymer solar cells.  相似文献   
989.
990.
【目的】丝状真菌里氏木霉是纤维素酶生产的主要工业真菌。纤维素酶分泌过程中的蛋白运输途径是控制大量纤维素酶成功输出的重要环节,因此,研究蛋白分泌途径的特定靶标基因功能将有助于鉴定纤维素酶运输分泌过程的关键调控因子。本研究借助基因敲除方法将里氏木霉液泡蛋白分选相关基因VPS13缺失,分析了该基因缺失对菌株生长、生孢尤其是纤维素酶分泌的影响。【方法】利用Double-joint PCR技术和同源重组策略构建里氏木霉VPS13基因缺失突变株,通过菌丝培养、显微观察、生孢检测、蛋白与酶活测定,系统比较VPS13基因敲除前后菌株的生长特征、菌丝形态、孢子形成、蛋白分泌以及纤维素酶活等。【结果】成功获得两株VPS13基因缺失株。与出发菌株相比,该基因突变后菌丝蔓延速率明显减慢,但菌体生物量在对数生长期后显著增多。通过显微观察,发现该基因缺失株菌丝更加密集,分支明显增多。此外,该基因缺失也导致菌株生孢延迟。纤维素底物平板分析发现VPS13基因缺失株菌落周围透明圈更加清晰,且透明圈圈径比是出发菌株的4倍,说明降解纤维素的能力有明显提高。进一步的液体发酵实验结果显示,该基因缺失导致蛋白产量及纤维素酶活力分别提高16.4%和21.9%。【结论】里氏木霉VPS13基因在菌丝生长、生孢、蛋白分泌等不同生物学过程中具有功能多样性,且该基因在菌种改良上可以作为提高纤维素酶产量的重要靶点。  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