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101.
米糠蛋白酶解物类阿片拮抗活性的研究 总被引:4,自引:0,他引:4
采用水解度(DH)对酶解米糠蛋白进行了研究,比较六种蛋白酶对米糠可溶性蛋白的水解作用,结果发现胰蛋白酶对米糠可溶性蛋白的水解作用最强,它的最适作用条件为:pH8.0,温度为37℃,[E]/[S]为12.5usp-u/kg。采用离体豚鼠回肠(GPI)检定法测定上述酶解物的类阿片拮抗活性,结果发现胰蛋白酶水解产物具有明显的类阿片拮抗活性,DH为11.9%时,其水解产物(样品A)的类阿片拮抗活性最高。体积排阻高效液相色谱测定它的相对分子质量分布范围在125-24233Da之间。 相似文献
102.
Four conditional responses (CRs) were measured in rats implanted with bilateral cannulas in the basolateral nuclear complex of the amygdala (BLA). During retention testing in either the original training context or a shifted context, BLA was infused with artificial cerebral spinal fluid (ACSF) or ACSF containing an N-methyl-D-aspartate receptor antagonist (APV). Regardless of the testing context, APV infusion into BLA completely blocked the expression of conditional eyeblink facilitation and significantly attenuated the expression of conditional freezing, ultrasonic vocalization, and defecation. Discriminant analysis found eyeblink facilitation to be comparable to freezing in predicting group membership (APV vs. ACSF) and both to be better predictors than the other two CRs. The APV effect did not depend on the exact cannula positions within BLA. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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104.
The authors investigated whether corticotropin-releasing factor (CRF) within the central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST) is a critical component of the neural circuitry mediating conditioned defeat. In this model, hamsters that have experienced social defeat subsequently display only submissive-defensive agonistic behavior instead of territorial aggression. Conditioned defeat was significantly reduced following infusion of the CRF receptor antagonist D-Phe CRF(12-41) into the BNST but not into the CeA. In another experiment, hamsters given unilateral lesions of the CeA and infusions of D-Phe CRF(12-41) into the contralateral BNST displayed significantly less submissive behavior than did controls. These data suggest that CRF acts within a neural circuit that includes the amygdala and the BNST to modulate agonistic behavior following social defeat. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
105.
This study examined whether the cannabinoid antagonist, SR 141716A, could be established as a discriminative stimulus in rhesus monkeys treated with Δ?-tetrahydrocannabinol (Δ?-THC). Stimulus control was established with SR 141716A (1.0 mg/kg) in 3 Δ?-THC-treated monkeys (1.12 mg/kg/day) in 113-124 sessions. The SR 141716A discriminative stimulus was dose related, attenuated by an acute injection of Δ?-THC, and not mimicked by cocaine or ketamine. SR 141716A-appropriate responding occasioned by temporary discontinuation of Δ?-THC treatment was attenuated by Δ?-THC and not ketamine. The SR 141716A discriminative stimulus in Δ?-THC-treated monkeys appears to be mediated by cannabinoid receptors and could be related to Δ?-THC withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
106.
尼伐地平属于第二代二氢吡啶类钙离子拮抗剂 ,其与Ca2 + 通道特异部位的结合力比硝苯地平强 10倍 ,作用持续时间较之长 2~ 3倍 ,血药浓度较为平稳 ,良好的降压作用能维持 2 4h以上。因此 ,尼伐地平是安全、有效的首选高血压治疗药物 ,其应用前景十分广阔 ,市场潜力十分巨大。 相似文献
107.
以乙酰乙酸甲氧基乙基酯、乙酰乙酸肉桂醇酯为起始原料,经中间体3-氨基巴豆酸肉桂醇酯,通过Aldol缩合、Hantzsch环合反应,合成出了钙离子拮抗剂西尼地平。该合成工艺安全可行,操作简单,适合工业化生产。 相似文献
108.
Miller Jonathan P.; McAuley J. Devin; Pang Kevin C. H. 《Canadian Metallurgical Quarterly》2006,120(1):162
Effects of MK-801, an N-methyl-D-aspartate antagonist, on short-interval timing were examined using the peak-interval (PI) and PI-gap procedures. Fisher 344 rats were given daily injections of 0.025 mg/kg, 0.05 mg/kg, and 0.2 mg/kg MK-801. The main results were (a) 0.2 mg/kg MK-801 produced an immediate overestimation of the criterion time; (b) MK-801 increased peak rate of responding; (c) 0.2 mg/kg MK-801 produced an increase in variability; (d) during the PI-gap procedure, a reset pattern was observed for all rats (MK-801 and saline). Results suggest that MK-801 has at least 2 effects. First, MK-801 interferes with short-interval timing by producing an overestimation of time and a nonscalar increase in variability. Second, MK-801 increases response rate, suggesting a decrease in response inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
109.
Blessy George Xia Wen Edgar A. Jaimes Melanie S. Joy Lauren M. Aleksunes 《International journal of molecular sciences》2021,22(12)
The organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) mediate the renal secretion of drugs. Recent studies suggest that ondansetron, a 5-HT3 antagonist drug used to prevent nausea and vomiting, can inhibit OCT2- and MATE1-mediated transport. The purpose of this study was to test the ability of five 5-HT3 antagonist drugs to inhibit the OCT2 and MATE1 transporters. The transport of the OCT2/MATE1 probe substrate ASP+ was assessed using two models: (1) HEK293 kidney cells overexpressing human OCT2 or MATE1, and (2) MDCK cells transfected with human OCT2 and MATE1. In HEK293 cells, the inhibition of ASP+ uptake by OCT2 listed in order of potency was palonosetron (IC50: 2.6 μM) > ondansetron > granisetron > tropisetron > dolasetron (IC50: 85.4 μM) and the inhibition of ASP+ uptake by MATE1 in order of potency was ondansetron (IC50: 0.1 μM) > palonosetron = tropisetron > granisetron > dolasetron (IC50: 27.4 μM). Ondansetron (0.5–20 μM) inhibited the basolateral-to-apical transcellular transport of ASP+ up to 64%. Higher concentrations (10 and 20 μM) of palonosetron, tropisetron, and dolasetron similarly reduced the transcellular transport of ASP+. In double-transfected OCT2-MATE1 MDCK cells, ondansetron at concentrations of 0.5 and 2.5 μM caused significant intracellular accumulation of ASP+. Taken together, these data suggest that 5-HT3 antagonist drugs may inhibit the renal secretion of cationic drugs by interfering with OCT2 and/or MATE1 function. 相似文献
110.
4‐Benzothiazole‐7‐hydroxyindolinyl Diaryl Ureas Are Potent P2Y1 Antagonists with Favorable Pharmacokinetics: Low Clearance and Small Volume of Distribution 下载免费PDF全文
Dr. Jennifer X. Qiao Tammy C. Wang Dr. Sheldon Hiebert Carol H. Hu Dr. William A. Schumacher Dr. Steven A. Spronk Charles G. Clark Dr. Ying Han Ji Hua Laura A. Price Hong Shen Dr. Silvi A. Chacko Dr. Gerry Everlof Jeffrey S. Bostwick Thomas E. Steinbacher Yi‐Xin Li Dr. Christine S. Huang Dr. Dietmar A. Seiffert Dr. Robert Rehfuss Dr. Ruth R. Wexler Dr. Patrick Y. S. Lam 《ChemMedChem》2014,9(10):2327-2343
Current antithrombotic discovery efforts target compounds that are highly efficacious in thrombus reduction with less bleeding liability than the standard of care. Preclinical data suggest that P2Y1 antagonists may have lower bleeding liabilities than P2Y12 antagonists while providing similar antithrombotic efficacy. This article describes our continuous SAR efforts in a series of 7‐hydroxyindolinyl diaryl ureas. When dosed orally, 4‐trifluoromethyl‐7‐hydroxy‐3,3‐dimethylindolinyl analogue 4 was highly efficacious in a model of arterial thrombosis in rats with limited bleeding. The chemically labile CF3 group in 4 was then transformed to various groups via a novel one‐step synthesis, yielding a series of potent P2Y1 antagonists. Among them, the 4‐benzothiazole‐substituted indolines had desirable PK properties in rats, specifically, low clearance and small volume of distribution. In addition, compound 40 had high i.v. exposure and modest bioavailability, giving it the best overall profile. 相似文献