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   3161篇
  免费   160篇
  国内免费   7篇
  2024年   8篇
  2023年   34篇
  2022年   109篇
  2021年   192篇
  2020年   104篇
  2019年   116篇
  2018年   129篇
  2017年   111篇
  2016年   138篇
  2015年   193篇
  2014年   214篇
  2013年   246篇
  2012年   242篇
  2011年   229篇
  2010年   121篇
  2009年   114篇
  2008年   171篇
  2007年   122篇
  2006年   101篇
  2005年   96篇
  2004年   87篇
  2003年   58篇
  2002年   61篇
  2001年   38篇
  2000年   35篇
  1999年   19篇
  1998年   12篇
  1997年   14篇
  1996年   8篇
  1995年   13篇
  1994年   12篇
  1993年   8篇
  1992年   24篇
  1991年   13篇
  1990年   11篇
  1989年   20篇
  1988年   11篇
  1987年   5篇
  1986年   6篇
  1984年   7篇
  1983年   7篇
  1982年   6篇
  1980年   8篇
  1979年   7篇
  1978年   5篇
  1977年   4篇
  1976年   4篇
  1975年   4篇
  1972年   6篇
  1971年   6篇
排序方式: 共有3328条查询结果,搜索用时 46 毫秒
991.
Alharbi  Fares  Tian  Yu-Chu  Tang  Maolin  Ferdaus  Md Hasanul  Zhang  Wei-Zhe  Yu  Zu-Guo 《Cluster computing》2021,24(2):1255-1275
Cluster Computing - Enterprise cloud data centers consume a tremendous amount of energy due to the large number of physical machines (PMs). These PMs host a huge number of virtual machines (VMs),...  相似文献   
992.
Biomechanics and Modeling in Mechanobiology - The present study has sought to investigate the fluid characteristic and mechanical properties of trabecular bone using fluid–structure...  相似文献   
993.
Landscape and Ecological Engineering - Riparian vegetation is constantly subjected to environmental stresses and reactive oxygen species (ROS) are generated in the plant tissue due to the stress....  相似文献   
994.
Primary effusion lymphoma (PEL) is an incurable non-Hodgkin's lymphoma and novel biology-based treatments are urgently needed in clinical settings. Shikonin (SHK), a napthoquinone derivative, has been used for the treatment of solid tumors. Here, we report that SHK is an effective agent for the treatment of PEL. Treatment with SHK results in significant reduction of proliferation in PEL cells and their rapid apoptosis in vitro. SHK-induced apoptosis of PEL cells is accompanied by the generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (Δψm), an activation of c-Jun-N-terminal kinase (JNK), p38, as well as caspase-3, -8, and -9. Scavenging of ROS in the presence of N-acetylcysteine (NAC) almost blocks the loss of mitochondrial membrane Δψm, activation of JNK, cleavage of caspase-3, -9, and an induction of apoptosis in SHK treated PEL cells. SP600125, a specific inhibitor of JNK, also rescues a proportion of cells from the apoptotic effect of SHK. In addition, inhibition of caspase activation in the presence of pan-caspase inhibitor, Q-VD-OPh, blocks the SHK-inducing apoptosis, but doesn't completely inhibit SHK-mediated JNK activation. Therefore, ROS is an upstream trigger of SHK-induced caspase dependent apoptosis of PEL cells through disruption of mitochondrial membrane Δψm in an intrinsic pathway and an activation of JNK in an extrinsic pathway. In a PEL xenografted mouse model, SHK treatment suppresses PEL-mediated ascites formation without showing any significant adverse toxicity. These results suggested that SHK could be a potent anti-tumor agent for the treatment of PEL.  相似文献   
995.
Bumblebee, Bombus terrestris queens undergo winter diapause and show a great difference in diapause duration in natural conditions. Queens emerged from diapause initiate colonies by producing a batch of diploid (fertilised) eggs that develop into workers. In this study we investigated the effects of both the duration of queen diapause (2, 3, 4, or 5 months) and colony size (artificially limited to 50, 100, 150, and 200 workers) on the number of sexuals (males or new queens — gynes) produced, when gynes are produced and the longevity of both the foundress queen and the colony. Both worker population and diapause duration showed significant effect on sexual gyne production, foundress queen longevity and colony longevity but their interaction effect was insignificant. The worker number and diapause duration, respectively showed significant effect on sexual male production and gyne emergence period, but their interaction effects were insignificant.  相似文献   
996.
Background: Helicobacter pylori (H. pylori) is a gram negative bacterium that can cause diseases such as peptic ulcers and gastric cancer. IL‐17A, a proinflammatory cytokine that can induce the production of CXC chemokines for neutrophil recruitment, has recently been shown to be elevated in both H. pylori‐infected patients and mice. Furthermore, studies in mouse models of vaccination have reported levels significantly increased over infected, unimmunized mice and blocking of IL‐17A during the challenge phase in immunized mice reduces protective immunity. Because many aspects of immunity had redundant or compensatory mechanisms, we investigated whether mice could be protectively immunized when IL‐17A function is absent during the entire immune response using IL‐17A and IL‐17A receptor knockout (KO) mice immunized against H. pylori. Materials and Methods: Gastric biopsies were harvested from naïve, unimmunized/challenged, and immunized/challenged wild type (WT) and KO mice and analyzed for inflammation, neutrophil, and bacterial levels. Groups of IL‐17A KO mice were also treated with anti‐IFNγ or control antibodies. Results: Surprisingly, all groups of immunized KO mice reduced their bacterial loads comparably to WT mice. The gastric neutrophil counts did not vary significantly between IL‐17A KO and WT mice, whereas IL‐17RA KO mice had on average a four‐fold decrease compared to WT. Additionally, we performed an immunization study with CXCR2 KO mice and observed significant gastric neutrophils and reduction in bacterial load. Conclusion: These data suggest that there are compensatory mechanisms for protection against H. pylori and for neutrophil recruitment in the absence of an IL‐17A‐CXC chemokine pathway.  相似文献   
997.
We have designed, synthesized, and tested conjugates of chemically modified luciferase siRNA (Luc-siRNA) with bi-, tri-, and tetravalent cyclic(arginine-glycine-aspartic) (cRGD) peptides that selectively bind to the αvβ3 integrin. The cellular uptake, subcellular distribution, and pharmacological effects of the cRGD-conjugated Luc-siRNAs compared to those of unconjugated controls were examined using a luciferase reporter cassette stably transfected into αvβ3 positive M21(+) human melanoma cells. The M21(+) cells exhibited receptor-mediated uptake of cRGD-siRNA conjugates but not of unconjugated control siRNA. The fluorophore-tagged cRGD-siRNA conjugates were taken up by a caveolar endocytotic route and primarily accumulated in cytosolic vesicles. The bi-, tri-, and tetravalent cRGD conjugates were taken up by M21(+) cells to approximately the same degree. However, there were notable differences in their pharmacological effectiveness. The tri- and tetravalent versions produced progressive, dose-dependent reductions in the level of luciferase expression, while the bivalent version had little effect. The basis for this divergence of uptake and effect is currently unclear. Nonetheless, the high selectivity and substantial "knock down" effects of the multivalent cRGD-siRNA conjugates suggest that this targeting and delivery strategy deserves further exploration.  相似文献   
998.
Galactofuranose (Galf) is the 5-member-ring form of galactose found in the walls of fungi including Aspergillus, but not in mammals. UDP-galactofuranose mutase (UgmA, ANID_3112.1) generates UDP-Galf from UDP-galactopyranose (6-member ring form). UgmA-GFP is cytoplasmic, so the UDP-Galf residues it produces must be transported into an endomembrane compartment prior to incorporation into cell wall components. ANID_3113.1 (which we call UgtA) was identified as being likely to encode the A. nidulans UDP-Galf transporter, based on its high amino acid sequence identity with A. fumigatus GlfB. The ugtAΔ phenotype resembled that of ugmAΔ, which had compact colonies, wide, highly branched hyphae, and reduced sporulation. Like ugmAΔ, the ugtAΔ hyphal walls were threefold thicker than wild type strains (but different in appearance in TEM), and accumulated exogenous material in liquid culture. AfglfB restored wild type growth in the ugtAΔ strain, showing that these genes have homologous function. Immunostaining with EBA2 showed that ugtAΔ hyphae and conidiophores lacked Galf, which was restored in the AfglfB-complemented strain. Unlike wild type and ugmAΔ strains, some ugtAΔ metulae produced triplets of phialides, rather than pairs. Compared to wild type strains, spore production for ugtAΔ was reduced to 1%, and spore germination was reduced to half. UgtA-GFP had a punctate distribution in hyphae, phialides, and young spores. Notably, the ugtAΔ strain was significantly more sensitive than wild type to Caspofungin, which inhibits beta-glucan synthesis, suggesting that drugs that could be developed to target UgtA function would be useful in combination antifungal therapy.  相似文献   
999.
Meat-type chickens show high feed efficiency and have a very rapid growth rate compared with laying-type chickens. To clarify whether the type-specific difference in feed conversion efficiency is involved in mitochondrial bioenergetics, modular kinetic analysis was applied to oxidative phosphorylation in skeletal muscle mitochondria of both type chickens. Mitochondria from skeletal muscle of meat-type chickens showed greater substrate oxidation and phosphorylating activities, and less proton leak than those of the laying-type, resulting in a higher efficiency of oxidative phosphorylation. Gene expression and protein content of uncoupling protein (avUCP) but not adenine nucleotide translocase (avANT) gene expression were lower in skeletal muscle mitochondria of meat-type chickens than the laying-type. The current results regarding a higher efficiency of oxidative phosphorylation and UCP content may partially support the high feed efficiency of meat-type chickens.  相似文献   
1000.
A sensitive fluorescence (FL) technique is proposed for the determination of levofloxacin (LVX). The method is based on the fact that the weak FL signal of the Tb(III)–LVX system is strongly enhanced in the presence of gold nanoparticles. Gold nanoparticles were prepared by the citrate reduction of HAuCl4 and characterized by transmission electron microscopy (TEM). Levofloxacin and Tb(III) ion form a fluorescence complex in aqueous solution, and its maximum emission wavelength was found at 545 nm. Optimal conditions for the formation of the levofloxacin–Tb(III) complexes were studied. Levofloxacin was detected by measuring the FL intensity, which increases linearly with the concentration of LVX in the range 6.2 × 10−10–2.6 × 10−8 mol/L. Recovery of the target analytes was > 96% with good quality parameters: linearity (r2 > 0.996), limit of detection (LOD) and limit of quantification (LOQ) values 2.1 × 10−10 mol/L and 7.2 × 10−10 mol/L, and run‐to‐run and day‐to‐day precisions with relative standard deviations (RSDs) around 3%. Thus, the proposed method can be successfully applied to the routine determination of levofloxacin in pharmaceutical preparations. Copyright © 2011 John Wiley & Sons, Ltd.  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