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51.
Organocatalytic and Scalable Synthesis of the Anti‐Influenza Drugs Zanamivir,Laninamivir, and CS‐8958 下载免费PDF全文
Yunsheng Li Prof. Dr. Dawei Ma 《Angewandte Chemie (International ed. in English)》2014,53(50):13885-13888
Zanamivir, laninamivir, and CS‐8958 are three neuraminidase inhibitors that have been clinically used to combat influenza. We report herein a novel organocatalytic route for preparing these agents. Only 13 steps are needed for the assembly of zanamivir and laninamivir from inexpensive D ‐araboascorbic acid by this synthetic route, which relies heavily on a thiourea‐catalyzed enantioselective Michael addition of acetone to tert‐butyl (2‐nitrovinyl)carbamate and an anti‐selective Henry reaction of the resulting Michael adduct with an aldehyde prepared from D ‐araboascorbic acid. The synthetic procedures are scalable, as evident from the preparation of more than 3.5 g of zanamivir. 相似文献
52.
Yuanyuan Lin Jing Xu Qianqian Jia Wei Sun Jia Fu Yanni Lv Shengli Han 《Journal of separation science》2020,43(13):2571-2578
Mas‐related G protein‐coupled receptor X2 was a mast cell–specific receptor mediating anaphylactoid reactions by activating mast cells degranulation, and it was also identified as a target for modulating mast cell–mediated anaphylactoid and inflammatory diseases. The anti‐anaphylactoid drugs used clinically disturb the partial effect of partial mediators released by mast cells. The small molecule of Mas‐related G protein‐coupled receptor X2 specific antagonists may provide therapeutic action for the anaphylactoid and inflammatory diseases in the early stage. In this study, the Mas‐related G protein‐coupled receptor X2 high expression cell membrane chromatography was coupled online with liquid chromatography and mass spectrometry and successfully used to screen anti‐anaphylactoid components from Magnolia biondii Pamp. Fargesin and pinoresinol dimethyl ether were identified as potential anti‐anaphylactoid components. Bioactivity of these two components were investigated by β hexosaminidase and histamine release assays on mast cells, and it was found that these two components could inhibit β hexosaminidase and histamine release in a concentration‐dependent manner. This Mas‐related G protein‐coupled receptor X2 high expression cell membrane chromatography coupled online with liquid chromatography and mass spectrometry system could be applied for screening potential anti‐anaphylactoid components from natural medicinal herbs. This study also provided a powerful system for drug discovery in natural medicinal herbs. 相似文献
53.
In this paper,we consider a possible modification of the de Sitter and anti-de Sitter space for the extended uncertainty principle.For the modified anti-de Sitter model we discuss the representation and wave functions of the momentum operator for a one-dimensional box problem.Also,we consider modified Snyder and anti-Snyder models for the generalized uncertainty principle.Then,we assume the Hamiltonian with different potential and solve the Heisenberg algebra for the modified(anti)-de Sitter and(anti)-Snyder models in both position and in the momentum space. 相似文献
54.
相转移催化法合成双3-苯丙烯酰基取代硫脲及双3-苯丙烯酰基取代胺衍生物 总被引:4,自引:0,他引:4
以3-苯丙烯酸为原料,经酰氯化,得到3-苯丙烯酰氯,在PEG-400为催化剂 的固液相转移催化条件下与硫氰酸铵及二胺类反应,一锅法制得双3-苯丙烯酰基 取代硫脲化合物。3-苯丙烯酰氯在PEG-600为催化剂的液液相转移催化条件下和 二胺类反应得到双-苯丙烯酰基取代胺化合物。反应条件温和、产率高。化合物经 元素分析、IR及^1H NMR证实。初步的生理活性研究表明,部分化合物具有良好的 抗炎活性。 相似文献
55.
Combined quantum mechanical calculations and classical molecular dynamics simulations were conducted to investigate the hydration properties of carboxybetaine zwitterion brushes with varying separation distances between the quaternary ammonium cation and carboxylic anion. The brushes consist of zwitterion trimers and are investigated to mimic interacting zwitterion chains grafted on a substrate as well as polymers with interacting zwitterion side chains. Our results show that the values of both positive and negative charges, their separation distances as well as chain interactions appear to play a critical role in the hydration properties of the zwitterions. The overall hydration property of these zwitterions is dictated by the competition between the strong hydration of the charged groups and the dehydration of the hydrocarbon chains. The strongest hydration occurs when the ? CH2? unit in the hydrocarbon chain reaches 6–8 for these trimers. Further increase in the hydrocarbon chain length to 10–14 leads to significant and sudden dehydration of the trimers. The water structure and the water residence time surrounding the zwitterions also demonstrate substantial alteration at this length scale. This hydrophilic‐to‐hydrophobic transition is induced by the hydrophobic interactions of the trimer chains. Our hydration results could explain the observed trend of the superiority of the methylated carbohydrates and poly(ethylene glycol) as antifouling materials compared to corresponding hydroxyl‐terminated compounds. © 2015 Wiley Periodicals, Inc. 相似文献
56.
氨基酸及其衍生物在止血/抗凝活性方面有一定的应用。以L-苯丙氨酸为起始原料,经磺化引入磺酸基,再与甲醇、乙醇、丙醇、异丙醇和正丁醇脱水酯化,一锅法合成了6种未见报道的L-苯丙氨酸的磺酸酯类衍生物(L1~L6),以期获得具有的较强血液生理活性的潜在药物。实验中采用了质谱、核磁共振进行结构表征。该合成方法产率高(78%~95%),后处理简单,不失为合成该类衍生物的好方法。衍生物的凝血四项实验表明:抗促凝效果是内源性和外源性凝血途径共同作用的结果。血浆复钙实验表明:衍生物均具有一定的抗凝活性,其抗凝效果随浓度变化而变化,但是随R链的长度增加,抗凝效果并未见规律性。衍生物的抗凝活性主要受磺酸基及酯基的影响,因此在设计合成抗血栓化合物时可以考虑引入磺酸基及酯类基团。 相似文献
57.
《Journal of heterocyclic chemistry》2017,54(2):1578-1589
Starting from pyrimidine‐2‐thiones, a set of new fused triazoles, thiazoles, and thiazines has been obtained. The mechanistic pathway and structures of all the novel products were ascertained on the foundation of spectral information and elemental analyses. The analgesic and anti‐inflammatory activities of all the prepared compounds were predestined. The outcomes disclosed that all of the examined samples revealed potent activity. Moreover, the relation between the structure and the activity has been researched. 相似文献
58.
列斐伏尔的"日常生活批判"揭示了消费社会的意识形态性,资产阶级通过对"日常生活"的建构,压制了人的革命性,掩盖了其剥削和压迫的强制性,使得剥削和压迫披上了理性外衣。要反抗这种异化,必须"让日常生活成为艺术品",摆脱日常行为异化的强制。"日常生活批判"释放了日常生活革命的可能性,戳穿了意识形态的虚假性,成为我们反抗现代物化与量化统治力量的新的革命起点。但由于缺乏马克思政治经济斗争支持,"日常生活"又失去其真正革命意义。 相似文献
59.
以ELISA检测108例活动性肺结核、39例稳定期肺结核、30例肿瘤、101例非结核性肺部疾病患者及202例正常人血清的抗结核菌纯蛋白衍生物(PPD)IgG抗体(简称抗-PPD)和循环免疫复合物(CIC)中的抗-PPDIgG抗体(简称CIC-PPD)。结果表明,活动性肺结核患者的抗-PPD和CIC-PPD水平明显高于正常人和各疾病组患者的水平(P<0.001),但与其病变范围无关。单一测定活动性肺结核患者的抗-PPD,敏感性为85.2%,特异性为98.5%;测定CIC-PPD,敏感性为86.1%.特异性96.9%。以两者任一项阳性作为诊断活动性肺结核的标准,则敏感性为93.5%。此外,对11例活动性肺结核患者的动态观察表明,随着治疗天数的增加和临床症状的改善,患者的抗-PPD和CIC-PPD水平会逐渐降低,前者于治疗后第20~24周降至正常水平,后者则于治疗后第12~16周降至正常值。研究结果提示测定患者的抗-PPD和CIC-PPD的水平,可用于结核病诊断,对结核病的疗效判定亦有帮助。 相似文献
60.
利用广义奇异值分解定理,得到了矩阵方程A^HXA=B的反自反解存在的一个充要条件,并获得了相应的通解表达式和最佳逼近解,最后获得了最小范数解。 相似文献