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目的:研究西青果多酚对甲基苯丙胺(Methamphetamine,METH)诱导大鼠肾上腺嗜铬细胞瘤(PC12)细胞损伤的保护作用及机制。方法:实验分为对照组、模型组(3 mmol/L METH)和不同浓度西青果多酚组(25、50、100、200 μg/mL西青果多酚+3 mmol/L METH),给药处理24 h后检测细胞存活率、细胞凋亡、细胞DNA损伤、超氧化物歧化酶(Superoxide dismutase,SOD)和谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)活力以及活性氧(Reactive oxygen species,ROS)和丙二醛(Malondialdehyde,MDA)含量等。结果:与对照组相比,3 mmol/L METH能极显著降低PC12细胞存活率(P<0.01),显著降低SOD和GSH-Px活力(P<0.05),显著增加胞内MDA含量(P<0.05),极显著增加细胞凋亡率、ROS含量和DNA损伤(P<0.01);与模型组相比,50~200 μg/mL西青果多酚能极显著抑制METH诱导的PC12细胞存活率和SOD活力的降低(P<0.01),显著抑制GSH-Px活力下降(P<0.05),极显著抑制METH导致的细胞凋亡、DNA损伤、胞内MDA和ROS含量增加(P<0.01)。结论:西青果多酚对METH诱导的PC12细胞损伤具有明显的保护作用,其作用机制可能与西青果多酚抑制METH诱导的氧化应激,缓解DNA损伤相关。 相似文献
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Qi L Gang L Hang KW Ling CH Xiaofeng Z Zhen L Wai YD Sang PW 《Microscopy research and technique》2011,74(12):1139-1144
Apoptosis and autophagy are the two major types of programmed cell death (PCD) in neurons. Homeostatic autophagy often precedes apoptosis, and when apoptosis is blocked, the failure to keep homeostasis will lead to necrosis instead. It has been reported that human immunodeficiency virus (HIV) infected methamphetamine (Meth) abusers represent greater neuropathological abnormalities than Meth abusers or HIV-positive non-Meth users. Recent publications suggest that Tat and Meth when administered together result in greater neuronal damage than when administered separately. However, the cellular events of the combined Tat-Meth effect have not yet been fully characterized. Therefore, we investigated the effects of Tat and/or Meth on apoptosis and autophagy to elucidate whether PCD was involved in Tat and/or Meth-induced neuronal damage. Annexin-V-FITC/PI staining assay was used to detect cellular apoptosis using a neuroblastoma cell line SH-SY5Y. Cellular ultrastructural changes were observed under transmission electron microscopy (TEM). Flow-cytometric data showed apoptosis following Meth treatment, and more extensive apoptosis with Tat + Meth treatment. The most important finding was that the autophagosome and/or multilamellar bodies (MLBs) were most pronounced with Tat + Meth treatment, were less so with Meth treatment, and infrequent with Tat treatment. This suggests the involvement of autophagy and apoptosis in Tat with Meth-elicited cell damage. However, the relation between apoptosis and autophagy remains unknown in this experiment. Further research is needed to analyze the relation among related molecules. A thorough understanding of this multifaceted relationship will be critical for the assessment of therapeutic modalities for patients with HIV with drug abuse. 相似文献
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Molecular Containers Bind Drugs of Abuse in Vitro and Reverse the Hyperlocomotive Effect of Methamphetamine in Rats 下载免费PDF全文
Shweta Ganapati Stephanie D. Grabitz Steven Murkli Flora Scheffenbichler Maíra I. Rudolph Dr. Peter Y. Zavalij Prof. Dr. Matthias Eikermann Prof. Dr. Lyle Isaacs 《Chembiochem : a European journal of chemical biology》2017,18(16):1583-1588
We measured the affinity of five molecular container compounds (calabadions 1 and 2 , CB[7], sulfocalix[4]arene, and HP‐β‐CD) toward seven drugs of abuse in homogenous aqueous solution at physiological pH by various methods (1H NMR, UV/Vis, isothermal titration calorimetry [ITC]) and found binding constants (Ka values) spanning from <102 to >108 m ?1. We also report X‐ray crystal structures of CB[7] ? methamphetamine and 1? methamphetamine. We found that 2 , but not CB[7], was able to ameliorate the hyperlocomotive activity of rats treated with methamphetamine. The bioavailability of the calabadions and their convergent building block synthesis suggest potential for further structural optimization as reversal agents for intoxication with nonopioid drugs of abuse for which no treatments are currently available. 相似文献
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Quinteros-Mu?oz David; Sáez-Briones Patricio; Díaz-Véliz Gabriela; Mora-Gutiérrez Sergio; Rebolledo-Fuentes Marco; Cassels Bruce K. 《Canadian Metallurgical Quarterly》2010,124(5):662
3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”) is a psychoactive drug structurally related to other phenylisopropylamines acting as stimulants or hallucinogens in humans. Although MDMA has a pharmacological identity of its own, the distinction of its acute effects from those of stimulants or even hallucinogens is controversial. In this work, dose-response curves (0.25, 0.5, 1, 3, 5, and 10 mg/kg) representing the acute in vivo effects of MDMA were compared with those of a structurally related stimulant (methamphetamine, MA) and a hallucinogenic analogue (2,5-dimethoxy-4-iodoamphetamine, DOI) in a set of behavioral protocols in rats, including spontaneous psychomotor activity, anxiolytic/anxiogenic-like effects and active avoidance conditioning responses. The behavioral profiles obtained allowed us to differentiate among racemic MDMA, MA, and DOI at different dose ranges. In addition, the evaluation of four MDMA analogues (1, 5, and 10 mg/kg) comprising two well-known MDMA analogues (MDA [3,4-methylenedioxyamphetamine] and MDE (N-ethyl-MDA, believed to substitute for MDMA) and two other structural analogues (MDOH [N-hydroxy-MDA] and MMDA-2 [2-methoxy-4,5-methylenedioxyamphetamine]) showed that none of these exactly resembles MDMA in their pharmacological profiles, highlighting the unique character of this prototypical entactogen. In fact, their effects exhibited similarities with the behavioral profiles of either MA or DOI, as well as novel profiles in specific behavioral paradigms. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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Reports an error in "Taste reactivity responses elicited by cocaine-, phencyclidine-, and methamphetamine-paired sucrose solutions" by Linda A. Parker (Behavioral Neuroscience, 1993[Feb], Vol 107[1], 118-129). Table 1, on page 119, contains two errors. In the first section, the dose/route for the agent nicotine should read as follows: 1.2-2.0 mg/kg sc. In the second section, the dose/route for the agent morphine should read as follows: 2-80 mg/kg ip. Also, on page 121, paragraph 3, line 14, the parenthetical information after 40 mg/kg cocaine should read (40C; 2 × 20 mg/kg/3 cc). (The following abstract of the original article appeared in record 1993-24959-001.) The nature of flavor–drug associations produced by a range of doses of the reinforcing agents cocaine (5, 10, 15, 20, or 40 mg/kg, sc), phencyclidine (0.5, 2, 10, or 20 mg/kg, sc), and methamphetamine (2, 5, or 10 mg/kg, ip) were assessed by the taste reactivity (TR) test and the conditioned taste avoidance (CTA) test. Even at the highest doses tested, none of the agents produced aversive TR responding. At doses that produced equivalent-strength CTA, lithium did establish aversive TR responding. Results provide evidence that drugs that serve as reinforcers in other paradigms produce conditioned flavor avoidance that is not motivated by a conditioned dislike for the flavor. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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