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A novel series of triazole-based compounds have been designed, synthesised and evaluated as multi-target-directed ligands (MTDLs) against Alzheimer disease (AD). The triazole-based compounds have been designed to target four major AD hallmarks that include Aβ aggregation, metal-induced Aβ aggregation, metal dys-homeostasis and oxidative stress. Among the synthesised compounds, 6n having o-CF3 group on the phenyl ring displayed most potent inhibitory activity (96.89% inhibition, IC50 = 8.065 ± 0.129 μM) against Aβ42 aggregation, compared to the reference compound curcumin (95.14% inhibition, IC50 = 6.385 ± 0.009 μM). Compound 6n disassembled preformed Aβ42 aggregates as effectively as curcumin. Furthermore, 6n displayed metal chelating ability and significantly inhibited Cu2+-induced Aβ42 aggregation and disassembled preformed Cu2+-induced Aβ42 aggregates. 6n successfully controlled the generation of the reactive oxygen species (ROS) by preventing the copper redox cycle. In addition, 6n did not display cytotoxicity and was able to inhibit toxicity induced by Aβ42 aggregates in SH-SY5Y cells. The preferred binding regions and key interactions of 6n with Aβ42 monomer and Aβ42 protofibril structure was evaluated with molecular docking. Compound 6n binds preferably to the C-terminal region of Aβ42 that play a critical role in Aβ42 aggregation. The results of the present study highlight a novel triazole-based compound, 6n, as a promising MTDL against AD. 相似文献
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ObjectiveThe effect of orange juice and Coca Cola® on the release of metal ions from fixed orthodontic appliances.Materials and methodsA continuous flow system designed for in vitro testing of orthodontic appliances was used. Orange juice/Coca Cola® was flowing through the system alternately with artificial saliva for 5.5 and 18.5 h, respectively. The collected samples underwent a multielemental ICP-OES analysis in order to determine the metal ions release pattern in time.ResultsThe total mass of ions released from the appliance into orange juice and Coca Cola® (respectively) during the experiment was calculated (μg): Ni (15.33; 37.75), Cr (3.604; 1.052), Fe (48.42; ≥156.1), Cu (57.87, 32.91), Mn (9.164; 41.16), Mo (9.999; 30.12), and Cd (0.5967; 2.173).ConclusionsIt was found that orange juice did not intensify the release of metal ions from orthodontic appliances, whereas Coca Cola® caused increased release of Ni ions. 相似文献
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Total knee arthroplasty is a well established treatment for degenerative joint disease, which is also performed as a treatment in younger and middle-aged patients who have a significant physical activity and high life expectancy. However, complications may occur due to biological responses to wear particles, as well as local and systemic hypersensitivity reactions triggered by metal ions and particles such as cobalt, chromium and molybdenum. The purpose of the study was to perform a highly demanding activities (HDA) knee wear simulation in order to compare the wear characteristics and metal ion release barrier function of a zirconium nitride (ZrN) coated knee implant, designed for patients with suspected metal ion hypersensitivity, against an uncoated knee implant made out of CoCrMo. The load profiles were applied for 5 million HDA cycles, which represent 15–30 years of in vivo service depending on the activity level of the patient. Results showed a significant wear rate reduction for the coated group (1.01 ± 0.29 mg/million cycles) in comparison with the uncoated group (2.89 ± 1.04 mg/million cycles). The zirconium nitride coating showed no sign of scratches nor delamination during the wear simulation, whereas the uncoated femurs showed characteristic wear scratches in the articulation areas. Furthermore, the metal ion release from the coated implants was reduced up to three orders of magnitude in comparison with the uncoated implants. These results demonstrate the efficiency of zirconium nitride coated knee implants to reduce wear as well as to substantially reduce metal ion release in the knee joint. 相似文献
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Elena Frati Abdel-Majid Khatib Philippe Front Andrej Panasyuk France Aprile Dragoslav R. Mitrovic 《Free radical biology & medicine》1997,22(7):1139-1144
The effect of photoexcited riboflavin (RF) on the viscosity of hyaluronic acid (HA) solutions has been investigated. UV irradiation of RF causes under aerobic conditions fragmentation of HA and a decrease in the viscosity of its solutions. A decrease of HA viscosity occurs in PO4-buffered solutions and is accelerated by high pH, Fe2+ (but much less so by Fe3+), certain metal chelators, and horseradish peroxidase (HRP); it is partially inhibited by catalase and less so by superoxide dismutase (SOD). The reactivity of the system was completely blocked by Tris, ethanol, aspirin, d-manitol, dimethylthiourea (DMTU), dimethylsulfoxide (DMSO), and sodium azide. These results indicate that the most likely chemical species involved in the reaction is the hydroxyl radical. Singlet oxygen (102) generation is suggested by the ability of NaN3 and DMSO to completely inhibit the reactivity of the system. These two agents, however, may also interact with OH√ radical, as well and suppress the reactivity of the system. H2O2 and
seem also to be produced in significant amounts, because catalase and SOD partially block the reactivity of the system. The effect of HRP may be due to hydrogen subtraction from HA and H2O2 reduction to water. Photoexcitation of RF may potentially occur in vitro and in vivo in the organs and tissues that are permeable to light, such as the eye or skin, and damage HA and other cell-matrix components causing inflammation and accelerating aging. © 1997 Elsevier Science Inc. 相似文献
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Cd2+、Al3+作用下蚕豆UDS与微核相关性分析及高等植物UDS技术初探 总被引:2,自引:1,他引:1
为探讨金属离子对高等植物非按期DNA合成(UnscheduledDNASythesis,简称UDS)和微核(MCN)的诱导作用、二者之间的关联性以及利用高等植物UDS技术检测环境诱变物的可行性,利用3HTdR前体掺入法研究了Cd2+、Al3+作用下蚕豆的UDS效应。结果表明,Cd2+、Al3+均能不同程度地诱导蚕豆UDS和MCN的发生;UDS量与微核率(MCNF)之间呈负相关(r<0),但相关不显着(|r|0.05),且二者间的相关程度在Cd2+和Al3+两种金属离子作用下没有显着差别(P>0.05);利用高等植物UDS技术检测环境诱变物质,在一定受检物剂量范围内是可靠的,但超过这个剂量范围,UDS技术无法检出. 相似文献
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Cu~(2+)、Pb~(2+)和Cd~(2+)对荞麦种子中抗氧化酶活性的影响 总被引:14,自引:0,他引:14
近年来,有关荞麦降血脂、降血糖和抗衰老等的作用引起国内外生化、营养和医药学界的普遍关注[1,2].一些研究表明,荞麦中富含超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)等能够清除机体内超氧阴离子自由基(O-·2)、羟自由基(·OH)和H2O2等有害物质?.. 相似文献