全文获取类型
收费全文 | 2336篇 |
免费 | 94篇 |
国内免费 | 229篇 |
专业分类
化学 | 2480篇 |
晶体学 | 6篇 |
力学 | 4篇 |
综合类 | 23篇 |
数学 | 12篇 |
物理学 | 134篇 |
出版年
2024年 | 2篇 |
2023年 | 34篇 |
2022年 | 147篇 |
2021年 | 168篇 |
2020年 | 92篇 |
2019年 | 77篇 |
2018年 | 55篇 |
2017年 | 53篇 |
2016年 | 86篇 |
2015年 | 93篇 |
2014年 | 86篇 |
2013年 | 189篇 |
2012年 | 232篇 |
2011年 | 143篇 |
2010年 | 102篇 |
2009年 | 119篇 |
2008年 | 143篇 |
2007年 | 132篇 |
2006年 | 110篇 |
2005年 | 107篇 |
2004年 | 88篇 |
2003年 | 63篇 |
2002年 | 85篇 |
2001年 | 25篇 |
2000年 | 27篇 |
1999年 | 29篇 |
1998年 | 27篇 |
1997年 | 22篇 |
1996年 | 21篇 |
1995年 | 19篇 |
1994年 | 12篇 |
1993年 | 9篇 |
1992年 | 10篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1959年 | 1篇 |
排序方式: 共有2659条查询结果,搜索用时 218 毫秒
51.
GABAA五种亚型受体与BZ配基的3D-QSAR研究 总被引:1,自引:0,他引:1
GABAA受体是中枢神经系统内重要的抑制性受体,有广泛的神经生理活性.由于镇静/抗惊厥药物在临床上的广泛应用,使得其中苯并二氮杂作用位点尤为重要.我们用比较分子场法(CoMFA)对一系列咪唑苯并二氮杂类化合物(BZ)与五种重组受体亚型的亲和力进行了结构活性关系研究,得到的一组模型都有较高的交叉验证系数.并在此基础上,建立了非交叉验证的一组PLS模型.用该组模型对随机选择的6个化合物组成的测试集进行了预测,都得到了相当满意的结果,表明所建立的一组模型具有良好的预测能力.本研究对于设计高亲和力的BZ受体的配基和研究GABAA受体的模型有指导意义. 相似文献
52.
de Oliveira Neto Marçal Pires José M. Giambiagi Mario de Giambiagi Myriam Segre Alvarez Fernando A. 《Structural chemistry》1998,9(5):339-348
Electronic properties of lamotrigine (LTG) and two analogues (A1 and A2) are compared through MOPAC-AM1 calculations. Two stable conformers of LTG are calculated to exist in agreement with X-ray crystallography. In the three compounds and the two conformers for each of them, the more favorable protonation sites are N2 and N4; these should then be the sites appropriate for interaction with a receptor, and group valence reinforces the supposition. The molecular electrostatic potentials show that a region between the two chlorine atoms in LTG could be the site for an electrostatic interaction with a corresponding site in the receptor. The fluorine atom in A1 would play an equivalent role. A simple model for LTG-receptor interaction is proposed. 相似文献
53.
Proper epidemiological, risk assessment and exposure analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related halogenated aromatic hydrocarbons (HAHs) requires accurate measurements of these chemicals both in the species of interest and in various exposure matrices (i.e. biological, environmental, food and feed). High-resolution instrumental analysis techniques are established for these chemicals, however, these procedures are very costly and time-consuming and as such, they are impractical for large scale sampling studies (i.e. for epidemiological studies and assessment of areas with widespread contamination). Accordingly, numerous bioanalytical methods have been developed for the detection of these chemicals in extracts from a variety of matrices, the majority of which take advantage of the ability of these chemicals to activate the aromatic hydrocarbon receptor (AhR) and the AhR signal transduction pathway. Here we review the currently available in vitro AhR-based cell bioassay systems with a focus on recent recombinant reporter gene cell lines that have been developed for detection and relative quantitation of TCDD and related HAHs. Comparison of the relative sensitivities of the various cell bioassays and examples of their use in screening and analysis of environmental, biological, and food and feed samples are presented. Currently available experimental results and validation studies demonstrate the utility of these cell bioassay systems to provide a relatively rapid, accurate, and cost effective screening approach for the detection of TCDD and related HAHs in a variety of environmental, biological, food and feed samples. The availability of these cell bioassay systems will not only facilitate the large scale sampling studies needed for accurate assessment of contamination and exposure to these environmental chemicals, but they provide avenues for the identification of novel classes of TCDD-like chemicals. 相似文献
54.
酶联免疫吸附法直接测定血清雌二醇 总被引:20,自引:0,他引:20
本合成了3种不同载体蛋白的雌二醇抗原,研究了载体蛋白免疫原性对雌二醇抗体产生的影响。应用酶联免疫吸附分析法测定了血清中雌二醇,浓度范围为5-160ng/ml(1.8×10^-^8-5.9×10^-^7mol/L).RSD%小于10.%,检测限为1.97ng/ml,相当于98.5pg/孔(按空白平均值的二倍标准偏差计算)。另外,本还建立了一种用考马斯亮蓝G-250测定半抗原与蛋白结合比的方法,提 相似文献
55.
Molt O Rübeling D Schäfer G Schrader T 《Chemistry (Weinheim an der Bergstrasse, Germany)》2004,10(17):4225-4232
Host molecule 1 displays a high affinity in water towards catecholamines and especially related structures such as beta-blockers with extended aromatic pi-faces (up to 7x10(3) M(-1) for each single complexation step or 5x10(7) M(-2) for both steps). The amphiphilic structural design leads to an extensive self-association of host molecules through their aromatic flanks. Above a cmc (critical micelle concentration) of 3x10(-4) M, host 1 forms micelles that produce a favorable microenvironment for hydrophobic interactions with the included guest molecules. Electrostatic attraction of the ammonium alcohol by the phosphonate anions is thus combined with hydrophobic contributions between the aromatic moieties. Ionic hydrogen bonds with polar OH or NH groups of the guest enforce the non-covalent interactions, and finally lead to increased specificity. Both its affinity and its selectivity towards adrenergic receptor substrates are greatly enhanced if the receptor molecule 1 is transferred from water into a lipid monolayer. Catecholamines and beta-blockers lead to drastically different effects at concentrations approaching the micromolar regime. Especially beta-blockers with minute structural changes can be easily distinguished from each other. In both cases, extensive hydrophobic interactions with a self-associated and/or self-organized microenvironment are largely responsible for the observed high efficiency and specificity. 相似文献
56.
Joanna Gajewiak 《Tetrahedron letters》2006,47(43):7607-7609
Lysophosphatidic acid (LPA) and phosphatidic acid (PA) are potent bioactive lipid mediators of signal transduction and are inactivated by phosphatases. To obtain receptor-isoform selective ligands with neutral phosphomimetic head groups, we performed the stereoselective synthesis of LPA and PA analogues with trifluoromethanesulfonamide and trifluoromethanesulfonamidoxy moieties replacing the phosphomonoester. 相似文献
57.
Determining PPARγ-ligand binding affinity using fluorescent assay with cis-parinaric acid as a probe
Gao Zhenting Luo Haibin Chen Lili Shen Jianhua CHEN Kaixian JIANG Hualiang SHEN Xu 《中国科学B辑(英文版)》2005,48(2)
Upon the study of small-molecules binding to proteins, the traditional methods for calculating dissociation constants (Kd and Ki) have shortcomings in dealing with the single binding site models. In this paper, two equations have been derived to solve this problem. These two equations are independent of the total concentration or initial degree of saturation of receptor and the activity of the competitive molecule. Through nonlinear fitting against these two equations, Kd value of a probe can be obtained by binding assay, and Ki value of a ligand can be obtained by competitive assay. Moreover, only the total concentrations of receptor([R]t), ligand([L]t) and probe([P]t) are required for the data fitting. In this work, Ki values of some typical ligands of PPARγ were successfully determined by use of our equations, among which the Ki value of PPARγ-LY171883 was reported for the first time. 相似文献
58.
Abstract Aloe vera leaf contains some bioactive compounds that have a strong binding affinity toward estrogen receptor as compared to standard drug tamoxifen. In this study, we have found that the IC50 of Aloe vera leaf extract against breast cancer cell line (MCF-7) is 23?µg/mL which is much lower than the IC50 (332?µg/mL) of Aloe vera leaf extract against non-cancerous cell line (NIH-3T3). We have also calculated the total concentration of phenolic acid (385.662?µg/mL), flavonoids (160.402?µg/mL) and alkaloids (276.754?µg/mL) in Aloe vera leaf extract. The free radical scavenging activity of Aloe vera leaf extract is 67% to 89% (at 50 to 300?µg/ml). Our virtual molecular docking study suggests that bioactive compounds like Aloe-emodin (?8.8?Kcal/mol), 7-hydroxy-2,5 dimethylchromone (?7.5?Kcal/mol), Beta-sitosterol (?7.3?Kcal/mol) etc. have a greater binding affinity toward estrogen alpha receptor as compared to standard drug Tamoxifen (?6.4?Kcal/mol). 相似文献
59.
镍(Ⅱ)—p—MPAQ络合物极谱吸附波研究 总被引:1,自引:0,他引:1
5-[(对-甲基苯基)偶氮]-8-氨基喹啉(p-MPAQ)的合成及其在光度和荧光分析中的应用已有报道,但对其电化学性质未作研究,本文研究了p-MPAQ的极谱行为,在pH6.8的醋酸铵缓冲溶液中,p-MPAQ在-0.55 V呈现一示波极谱波(P_1),当有Ni~(2+)存在时,在-0.93V处出现一新峰(P_2),加0.0011%Triton X-100后,P_2波高明显增加实验证实该波为络合物 相似文献
60.
受体生物传感器的研究进展 总被引:2,自引:0,他引:2
综述了利用各种生物材料中的膜受体蛋白作为分子识别元件的受体生物传感器研究的最新进展。主要从离体受体传感器、细胞受体传感器和神经组织受体传感器3个方面,讨论了它们的特点和存在的问题,并展望了受体生物传感器未来的发展方向。共引用文献42篇。 相似文献