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   1370篇
  免费   92篇
  国内免费   4篇
  1466篇
  2024年   4篇
  2023年   27篇
  2022年   60篇
  2021年   97篇
  2020年   91篇
  2019年   166篇
  2018年   98篇
  2017年   78篇
  2016年   82篇
  2015年   72篇
  2014年   87篇
  2013年   123篇
  2012年   108篇
  2011年   88篇
  2010年   57篇
  2009年   50篇
  2008年   45篇
  2007年   18篇
  2006年   26篇
  2005年   20篇
  2004年   20篇
  2003年   19篇
  2002年   16篇
  2001年   1篇
  2000年   2篇
  1999年   1篇
  1998年   1篇
  1997年   1篇
  1996年   1篇
  1995年   1篇
  1994年   2篇
  1992年   1篇
  1988年   2篇
  1985年   1篇
排序方式: 共有1466条查询结果,搜索用时 15 毫秒
991.
The NMR solution structures of NTX-1 (PDB code 1W6B and BMRB 6288), a long neurotoxin isolated from the venom of Naja naja oxiana, and the molecular dynamics simulation of these structures are reported. Calculations are based on 1114 NOEs, 19 hydrogen bonds, 19 dihedral angle restraints and secondary chemical shifts derived from 1H to 13C HSQC spectrum. Similar to other long neurotoxins, the three-finger like structure shows a double and a triple stranded beta-sheet as well as some flexible regions, particularly at the tip of loop II and the C-terminal tail. The solution NMR and molecular dynamics simulated structures are in good agreement with root mean square deviation values of 0.23 and 1 A for residues involved in beta-sheet regions, respectively. The overall fold in the NMR structure is similar to that of the X-ray crystallography, although some differences exist in loop I and the tip of loop II. The most functionally important residues are located at the tip of loop II and it appears that the mobility and the local structure in this region modulate the binding of NTX-1 and other long neurotoxins to the nicotinic acetylcholine receptor.  相似文献   
992.
Applications of genetic constructs with multiple promoters, which are fused with reporter genes and simultaneous monitoring of various events in cells, have gained special attention in recent years. Lentiviral vectors, with their distinctive characteristics, have been considered to monitor the developmental changes of cells in vitro. In this study, we constructed a novel lentiviral vector (FUM-M), containing two germ cell-specific promoters (Stra8 and c-kit), fused with ZsGreen and DsRed2 reporter genes, and evaluated its efficiency in different cells following treatments with retinoic acid and DMSO. Several cell lines (P19, GC-1 spg and HEK293T) were transduced with this vector, and functional capabilities of the promoters were verified by flow cytometry and quantitative RT-PCR. Our results indicate that FUM-M shows dynamic behavior in the presence and absence of extrinsic factors. A correlation was also observed between the function of promoters, present in the lentiviral construct and the endogenous level of the Stra8 and c-kit mRNAs in the cells. In conclusion, we recommend this strategy, which needs further optimization of the constructs, as a beneficial and practical way to screen chemical inducers involved in cellular differentiation toward germ-like cells.  相似文献   
993.
994.
6-Hydroxydopamine (6-OHDA), a metabolite of dopamine is known to induce dopaminergic cell toxicity which makes that a suitable agent inducing an experimental model of Parkinson’s disease (PD). Agmatine has been shown to protect against some cellular and animal PD models. This study was aimed to assess whether agmatine prevents 6-OHDA-induced SH-SY5Y cell death and if yes, then how it affects Akt/glycogen synthesis kinase-3β (GSK-3β) and extracellular signal-regulated kinases (ERK) signals. The cells were treated with different drugs, and their viability was examined via MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay and morphological observation. Western blot studies were done to assess cleaved caspase-3, Akt/GSK-3β, and ERK proteins. 6-OHDA-induced cell death and caspase-3 cleavage, while agmatine prevented those changes. 6-OHDA also decreased the amount of phosphorylated Akt (pAkt)/Akt while increased GSK-3β activity which was prevented by agmatine. Additionally, this toxin increased pERK/ERK ratio which was averted again by agmatine. The PI3/Akt inhibitor, LY294002, impeded the changes induced by agmatine, while ERK inhibitor (PD98059) did not disturb the effects of agmatine, and by itself, it preserved the cells against 6-OHDA toxicity. This study revealed that agmatine is protective in 6-OHDA model of PD and affects Akt/GSK-3β and ERK pathways.  相似文献   
995.
Organophosphorus (OP) compounds are one of the most hazardous chemicals used as insecticides/pesticide in agricultural practices. A large variety of OP compounds are hydrolyzed by organophosphorus hydrolases (OPH; EC 3.1.8.1). Therefore, OPHs are among the most suitable candidates that could be used in designing enzyme-based sensors for detecting OP compounds. In this work, a novel nanobiosensor for the detection of paraoxon was designed and fabricated. More specifically, OPH was covalently embedded onto chitosan and the enzyme–chitosan bioconjugate was then immobilized on negatively charged gold nanoparticles (AuNPs) electrostatically. The enzyme was immobilized on AuNPs without chitosan as well, to compare the two systems in terms of detection limit and enzyme stability under different pH and temperature conditions. Coumarin 1, a competitive inhibitor of the enzyme, was used as a fluorogenic probe. The emission of coumarin 1 was effectively quenched by the immobilized Au-NPs when bound to the developed nanobioconjugates. However, in the presence of paraoxon, coumarin 1 left the nanobioconjugate, leading to enhanced fluorescence intensity. Moreover, compared to the immobilized enzyme without chitosan, the chitosan-immobilized enzyme was found to possess decreased Km value by more than 50%, and increased Vmax and Kcat values by around 15% and 74%, respectively. Higher stability within a wider range of pH (2–12) and temperature (25–90°C) was also achieved. The method worked in the 0 to 1050?nM concentration ranges, and had a detection limit as low as 5?×?10?11 M.  相似文献   
996.
Journal of Plant Growth Regulation - In order to investigate the effect of wastewater on the soil minerals movement, irrigation water use efficiency (IWUE) and leaf nutrients uptake of...  相似文献   
997.
Densification of thermally treated energy crops by torrefaction is required to increase the bulk density and to reduce the handling, transport, and storage cost for bioenergy applications. In this study, we investigated the densification characteristics of thermally treated energy cane and napier grass grown on marginal lands at various applied forces and binder levels. The addition of starch (0, 10, and 15%) and lignosulfonate (0, 5, and 10%) was examined to enhance the strength and durability of raw and torrefied briquettes, respectively. Although the use of starch binder relatively increased the bulk density, it did not improve the hardness and durability of untreated energy crop briquettes. The addition of 10% lignosulfonate binder increased the torrefied briquette density of up to 11% for energy cane and up to 38% for napier grass and decreased the compression energy by up to 35% for both samples. Moreover, the hardness (compressive resistance) was tripled, and the durability was relatively improved for both torrefied briquettes. The increase in applied force not only increased the bulk density but also increased the specific energy required for densification. However, there was no substantial change in hardness and durability when the compression force was increased from 15 to 20 kN for all samples. In overall, densification of thermally treated energy crops is required, and the quality of the briquettes can be improved by the use of appropriate binders for efficient handling, transport, and storage.  相似文献   
998.
Heat shock protein 90(Hsp90), as a molecular chaperone, play a crucial role in folding and proper function of many proteins. Hsp90 inhibitors containing isoxazole scaffold are currently being used in the treatment of cancer as tumor suppressers. Here in the present studies, new compounds based on isoxazole scaffold were predicted using a combination of molecular modeling techniques including three-dimensional quantitative structure–activity relationship (3D-QSAR), molecular docking and molecular dynamic (MD) simulations. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were also done. The steric and electrostatic contour map of CoMFA and CoMSIA were created. Hydrophobic, hydrogen bond donor and acceptor of CoMSIA model also were generated, and new compounds were predicted by CoMFA and CoMSIA contour maps. To investigate the binding modes of the predicted compounds in the active site of Hsp90, a molecular docking simulation was carried out. MD simulations were also conducted to evaluate the obtained results on the best predicted compound and the best reported Hsp90 inhibitors in the 3D-QSAR model. Findings indicate that the predicted ligands were stable in the active site of Hsp90.  相似文献   
999.
1000.
The present study provides the length–weight and length–length relationships information (LWR & LLR) for three Blenny species; Antennablennius adenensis from the coast of Larak Island in the Persian Gulf and Istiblennius pox and Omobranchus mekranensis, which were captured in the coasts of Chabahar city in the Gulf of Oman, Iran. Total length (TL) and standard length (SL) were determined as well as weight. Specimens were collected occasionally in summer 2017 and winter 2018 by Hand net. The length–weight parameter b for these species was 2.84, 3.29 and 3.06 respectively with a high coefficient of determination (r2 ≥ 0.95). All LLRs were highly correlated (r2 > 0.99). All three species had no previous report for LWR and LLR estimates in FishBase.  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