全文获取类型
收费全文 | 6786篇 |
免费 | 324篇 |
国内免费 | 286篇 |
出版年
2024年 | 11篇 |
2023年 | 82篇 |
2022年 | 153篇 |
2021年 | 163篇 |
2020年 | 223篇 |
2019年 | 319篇 |
2018年 | 319篇 |
2017年 | 210篇 |
2016年 | 216篇 |
2015年 | 177篇 |
2014年 | 426篇 |
2013年 | 688篇 |
2012年 | 200篇 |
2011年 | 414篇 |
2010年 | 227篇 |
2009年 | 287篇 |
2008年 | 297篇 |
2007年 | 319篇 |
2006年 | 266篇 |
2005年 | 276篇 |
2004年 | 249篇 |
2003年 | 226篇 |
2002年 | 189篇 |
2001年 | 113篇 |
2000年 | 87篇 |
1999年 | 91篇 |
1998年 | 83篇 |
1997年 | 106篇 |
1996年 | 110篇 |
1995年 | 84篇 |
1994年 | 65篇 |
1993年 | 71篇 |
1992年 | 67篇 |
1991年 | 52篇 |
1990年 | 30篇 |
1989年 | 42篇 |
1988年 | 27篇 |
1987年 | 35篇 |
1986年 | 29篇 |
1985年 | 36篇 |
1984年 | 73篇 |
1983年 | 41篇 |
1982年 | 51篇 |
1981年 | 31篇 |
1980年 | 31篇 |
1979年 | 35篇 |
1978年 | 11篇 |
1977年 | 19篇 |
1976年 | 12篇 |
1974年 | 14篇 |
排序方式: 共有7396条查询结果,搜索用时 15 毫秒
101.
Aysan Etemadi Salar Hemmati Mohammad Shahrivar-Gargari Yasaman Tamaddon Abibiglue Ahad Bavili Maryam Hamzeh-Mivehroud Siavoush Dastmalchi 《化学与生物多样性》2023,20(8):e202300075
Indanone derivatives containing meta/para-substituted aminopropoxy benzyl/benzylidene moieties were designed based on the structures of donepezil and ebselen analogs as the cholinesterase inhibitors. The designed compounds were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were measured. Inhibitory potencies (IC50 values) for the synthesized compounds ranged from 0.12 to 11.92 μM and 0.04 to 24.36 μM against AChE and BChE, respectively. Compound 5 c showed the highest AChE inhibitory potency with IC50 value of 0.12 μM, whereas the highest BChE inhibition was achieved by structure 7 b (IC50=0.04 μM). Structure-activity relationship (SAR) analysis revealed that there is no significant difference between meta and para-substituted derivatives in AChE and BChE inhibition. However, the most potent AChE inhibitor 5 c belongs to meta-substituted compounds, while the most active BChE inhibitor is para-substituted derivative 7 b . The order of enzyme inhibition potency based on the substituted amine group is dimethyl amine>piperidine>morpholine. Compounds containing C=C linkage are more potent AChE inhibitors than the corresponding saturated structures. Molecular docking studies indicated that 5 c interacts with AChE in a very similar way to that observed experimentally for donepezil. The introduced indanone-aminopropoxy benzylidenes could be used in drug-discovery against Alzheimer's disease. 相似文献
102.
103.
The benthic cyanobacterium Fischerella muscicola (Thur.) Gom. UTEX 1829 produces a secondary metabolite, fischerellin, that strongly inhibits other cyanobacteria and to a lesser extent members of the Chlorophyceae. Eubacteria are not affected. The major active compound is lipophilic and exhibits a molecular ion at m/z 408. It is heat- and acid-stable but decomposes in 1 M sodium hydroxide (80° C. 1 h). Fischerellin inhibits the photosynthetic but not the respiratory electron transport of cyanobacteria and chlorophytes. Its site of action is located in PS II. Two other species of Fischerella also produce fischerellin, indicating that the synthesis of such allelochemicals might be characteristic of the genus. 相似文献
104.
Aiko Kiso Koushi Hidaka Tooru Kimura Yoshio Hayashi Azin Nezami Ernesto Freire Yoshiaki Kiso 《Journal of peptide science》2004,10(11):641-647
Plasmepsin (Plm) has been identified as an important target for the development of new antimalarial drugs, since its inhibition leads to the starvation of Plasmodium falciparum. A series of substrate-based dipeptide-type Plm II inhibitors containing the hydroxymethylcarbonyl isostere as a transition-state mimic were synthesized. The general design principle was provision of a conformationally restrained hydroxyl group (corresponding to the set residue at the P2' position in native substrates) and a bulky unit to fit the S2' pocket. 相似文献
105.
Summary Using a combinatorial peptide library method, we identified YIYGSFK as an efficient and specific peptide substrate for pp60c-src protein tyrosine kinase (PTK) [Lam et al., Int. J. Pept. Protein Res., 45 (1995) 587]. Employing YIYGSFK as a template, we synthesized and evaluated a series of pseudosubstrate-based inhibitors for pp60c-src. We found that the efficiency of a given inhibitor was highly dependent on the specific tyrosine analog used at the phosphorylation site of the substrate. One of these pseudosubstrate inhibitors, YI(2-Nal)GSFK, selectively inhibited the kinase activity of pp60c-src, with a Ki of 24 M. This peptide inhibitor exhibited selectivity for pp60c-src as compared to other PTKs tested, such as c-Abl and Bcr-Abl. Our results suggest that selective inhibitors for a specific PTK can be developed when the structure of a specific and efficient small peptide substrate for this PTK can be used as a template for structure modification.Abbreviations 1-Nal
l-1-naphthylalanine
- 2-Nal
l-2-naphthylalanine
- BOP
benzotriazolyl-N-oxy-tris(dimethylamino)-phosphonium hexafluorophosphate
- BSA
bovine serum albumin
- cAPK
cyclic AMP-dependent protein kinase
- DIEA
diisopropylethylamine
- EGFR
epidermal growth factor receptor
- Fmoc
fluorenylmethoxycarbonyl
- HOBt
1-hydroxybenzotriazole
- MES
2-[N-morpholino]ethanesulfonic acid
- PBS
phosphate-buffered salts
- pCl
l-p-chlorophenylalanine
- pF
l-p-fluorophenylalanine
- PTK
protein tyrosine kinase
- TLC
thin-layer chromatography 相似文献
106.
全自动生化分析仪测定血清AST同工酶 总被引:1,自引:0,他引:1
应用天冬氨酸氨基转移酶抑制剂“AMANO-3”水解样品中的线粒体型天冬氨酸氨基转移酶同工酶(m-AST),测定血清中剩余的胞浆型AST同工酶(c-AST)活性,进而与总AST活性相比较并计算出受抑制剂水解的m-AST同工酶活性.由于此方法采用蛋白水解反应破坏m-AST,因此测定方法可直接应用于生化自动分析仪.亦建立了一个适于日立7150分析仪的AST同工酶联合测定方法.其测定和计算出的m-AST同工酶批内CV为3.5%~7.9%;其结果(y)与AST同工酶电泳迁移率(x)相关.y=1.019x-0.489,r=0.996(n=30).测定了113名健康人m-AST和c-AST,其m-AST参考值范围1.64~9.64U/L,x±s=(5.641±2.013)U/L;c-AST参考值范围5.69~16.81U/L,x±s=(5.641±2.013)U/L. 相似文献
107.
丝氨酸蛋白酶抑制剂的研究及应用 总被引:4,自引:0,他引:4
丝氨酸蛋白酶抑制剂(serpin)是一类结构、序列同源的蛋白酶抑制剂,它是体内许多蛋白水解级联反应的调节因子,其遗传性结构或分泌异常将导致许多疾病.因此对于其结构及作用机理的研究将为临床应用提供依据. 相似文献
108.
肝细胞增殖抑制因子(Hepaticproliferationinhibitor,HPI)粗制品、半纯品和纯品对体外培养的人肝癌细胞具有显著抑增殖作用,随样品纯度提高抑制活性逐渐增强。纯品(浓度5μg/ml)的抑制率达77.71%。正常成年大鼠肝细胞呈HPI阳性表达。在DEN诱发大鼠肝细胞癌的发生发展过程中,转化的癌前期细胞和肝癌细胞呈HPI阴性表达。表明肝细胞HPI的表达能力在其癌变过程中消失,从而失去了自身的抑癌作用。 相似文献
109.
110.
水稻巯基蛋白酶抑制剂(CPI)经用二硫苏糖醇,对氯汞苯甲酸和碘乙酸修饰后,对木瓜蛋白酶的抑制活性并无改变;用N-乙基顺丁烯二酰亚胺与CPI反应,可以测出CPI分子内有19个巯基被修饰,被修饰后,抑制活性仍无改变,表明水稻CPI的抑制活性不需要巯基参与;应用N-溴代丁二酰亚胺与CPI反应,可测出CPI分子内有2个Trp被修饰,修饰后,抑制活性全部丧失,表明Trp是保持抑制活性所必需的基团。水稻巯基蛋白酶抑制剂和丝氨酸蛋白酶抑制剂对稻瘟病菌丝体的生长均有抑制作用,但后者的抑制作用比前者更强,若将两种抑制剂混合使用,则对稻瘟病菌丝体的抑制作用非常强烈;当抑制剂加入量达72μg时,即可产生明显的抑制作用。 相似文献