全文获取类型
收费全文 | 11431篇 |
免费 | 930篇 |
国内免费 | 766篇 |
出版年
2024年 | 21篇 |
2023年 | 218篇 |
2022年 | 404篇 |
2021年 | 644篇 |
2020年 | 399篇 |
2019年 | 521篇 |
2018年 | 547篇 |
2017年 | 350篇 |
2016年 | 517篇 |
2015年 | 720篇 |
2014年 | 799篇 |
2013年 | 926篇 |
2012年 | 1077篇 |
2011年 | 937篇 |
2010年 | 572篇 |
2009年 | 495篇 |
2008年 | 533篇 |
2007年 | 492篇 |
2006年 | 427篇 |
2005年 | 361篇 |
2004年 | 302篇 |
2003年 | 225篇 |
2002年 | 187篇 |
2001年 | 202篇 |
2000年 | 170篇 |
1999年 | 174篇 |
1998年 | 101篇 |
1997年 | 123篇 |
1996年 | 105篇 |
1995年 | 87篇 |
1994年 | 91篇 |
1993年 | 48篇 |
1992年 | 74篇 |
1991年 | 55篇 |
1990年 | 44篇 |
1989年 | 46篇 |
1988年 | 38篇 |
1987年 | 27篇 |
1986年 | 19篇 |
1985年 | 22篇 |
1984年 | 12篇 |
1983年 | 9篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Chen SB Tan JH Ou TM Huang SL An LK Luo HB Li D Gu LQ Huang ZS 《Bioorganic & medicinal chemistry letters》2011,21(3):1004-1009
Discovery of potent and selective ligands for telomeric G-quadruplex DNA is a challenging work. Through a combination approach of pharmacophore model construction, model validation, database virtual screening, chemical synthesis and interaction evaluation, we discovered and confirmed triaryl-substituted imidazole TSIZ01 to be a new telomeric G-quadruplex ligand with potent binding and stabilizing activity to G-quadruplex DNA, as well as a 8.7-fold selectivity towards telomeric G-quadruplex DNA over duplex DNA. 相似文献
992.
Development of insect-resistant transgenic cotton with chimeric TVip3A* accumulating in chloroplasts
An optimized vip3A gene, designated as vip3A* was chemically synthesized and a thi1 gene chloroplast transit peptide coding sequence was attached to its 5′ end to produce the tvip3A*. vip3A* and tvip3A* genes were transformed into Gossypium hirsutum cv. Zhongmiansuo35. Of 42 independent transformants, 36 were positive for the vip3A* or tvip3A* gene. Four independent transgenic T1 lines with single-copy insertions and unchanged phenotypes (CTV1 and CTV2 for tvip3A*, and CV1 and CV2 for vip3A*) were selected by Southern blotting, and subjected to an insect bioassay and field assessment. Four homozygous T2 transgenic
lines were then selected and the amount of expressed Vip3A* protein was determined by western blotting and ELISA. The protein
concentrations of CTV1 and CTV2 were about three-fold higher than those of CV1 and CV2. As expected, the Vip3A* protein of
CTV1 and CTV2 were transported to the chloroplasts, where they accumulated. The Vip3A* protein concentration in the chloroplasts
of CTV1 and CTV2 was about 15-fold of that of CV1 and CV2. All four transgenic lines showed 100% mortality against fall armyworm
(Spodoptera frugiperda) and beet armyworm (Spodoptera exigua) by insect bioassay. Moreover, CTV1 and CTV2 exhibited 100% mortality against cotton bollworm (CBW, Helicoverpa zea), whereas CV1 and CV2 showed 75.0% and 72.5% mortality against CBW, respectively. The field bioassay indicated that CTV1
and CTV2 were more resistant to CBW than CV1 and CV2. Our results suggest that the two tvip3A* transgenic lines (CTV1 and CTV2) can be used to develop insect-resistant cultivars and could be used as a resource for raising
multi-toxins-expressing transgenic cotton. 相似文献
993.
A series of novel benzimidazole derivatives were designed, synthesized, and evaluated for their activities against four kinds of enteroviruses, that is, Coxsackie virus A16, B3, B6 and Enterovirus 71 in VERO cells. Strong activities against enterovirus replication and low cytotoxicities were observed in these benzimidazoles generally. The most promising compound was (l)-2-(pyridin-2-yl)-N-(2-(4-nitrophenyl)pentan-3-yl)-1H-benzimidazole-4-carboxamide (16), with a high antiviral potency (IC(50)=1.76 μg/mL) and a remarkable selectivity index (328). These compounds were selected for further evaluation as novel enterovirus inhibitors. 相似文献
994.
β-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes the initial step of fatty acid biosynthesis via a type II fatty acid synthase in most bacteria. The important role of this essential enzyme combined with its unique structural features and ubiquitous occurrence in bacteria has made it an attractive new target for the development of new FabH inhibitors. We first used a structure-based approach to develop 24 new vinylogous carbamates (4a-15a, 4b-15b) that target FabH for the development of new antibiotics in this paper. Potent FabH inhibitory and selective anti- Gram-negative bacteria activities were observed in most of these vinylogous carbamates. Especially, compound 6a and 7a showed the most potent FabH inhibitory activity with IC?? of 2.6 and 3.3 μM, respectively. Docking simulation was performed to position compound 6a into the Escherichia coli FabH active site and the possible binding conformation of compounds has been proposed. The biological data and molecular docking indicated that compounds 6a and 7a were potent inhibitors of E. coli FabH as antibiotics deserving further research. 相似文献
995.
A series of novel cinnamic acyl sulfonamide derivatives (9a-16e) have been designed and synthesized and their biological activities were also evaluated as potential tubulin polymerization inhibitors. Among all the compounds, 10c showed the most potent growth inhibitory activity against B16-F10 cancer cell line in vitro, with an IC(50) value of 0.8μg/mL. Docking simulation was performed to insert compound 10c into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. Based on the preliminary results, compound 10c with potent inhibitory activity in tumor growth may be a potential anticancer agent. 相似文献
996.
Yuan M Luo M Song Y Xu Q Wang X Cao Y Bu X Ren Y Hu X 《Bioorganic & medicinal chemistry》2011,19(3):1189-1196
Several recent developments suggest that the human glyoxalase I (GLO I) is a potential target for anti-tumor drug development. In present study, a series of curcumin derivatives with high inhibitory activity against human GLO I were discovered. Inhibition constant (K(i)) values of compounds 8, 9, 10, 11 and 13 to GLO I are 4.600μM, 2.600μM, 3.200μM, 3.600μM and 3.600μM, respectively. To elucidate the structural features of potent inhibitors, docking-based three-dimensional structure-activity relationship (3D-QSAR) analyses were performed. Satisfactory agreement between experiment and theory suggests that comparative molecular similarity index analysis (CoMSIA) modeling exhibit much better correlation and predictive power. The cross-validated q(2) value is 0.638 while no-validation r(2) value is 0.930. Integrated with docking-based 3D-QSAR CoMSIA modeling, molecular surface property (electrostatic and steric) mapping and molecular dynamics simulation, a set of receptor-ligand binding models and bio-affinity predictive models for rational design of more potent inhibitors of GLO I are established. 相似文献
997.
EBV裂解复制周期调控机制研究新进展 总被引:1,自引:0,他引:1
EBV与许多恶性疾病包括霍奇金病、伯基特淋巴瘤、鼻咽癌等恶性肿瘤发病有关人类B淋巴细胞是EBV天然宿主,其在宿主细胞中的生活周期分为潜伏感染和裂解感染。EBV潜伏感染时,为逃避宿主细胞的免疫杀伤,仅表达少量基因产物。而在外界条件如化学、物理或宿主细胞分化的刺激下,EBV可由潜伏感染进入到裂解复制(Lytic Replication)感染周期,促进病毒在宿主细胞中播散。根据EBV裂解复制产物出现的时间顺序可将裂解复制周期分为裂解复制立即早期、早期和晚期。1 EBV裂解复制不同时期产物的调控作用 相似文献
998.
蚕沙有机肥的养分特性及其肥效 总被引:2,自引:0,他引:2
将废弃蚕沙进行无害化处理和适度发酵开发出蚕沙有机肥,分析了其养分特点,并采用盆栽试验研究了蚕沙有机肥的肥效.结果表明:发酵蚕沙有机肥的全氮、全磷、全钾含量与堆肥前相比显著提高,分别比堆肥前提高了58.0%、84.4%和29.7%;添加微生物菌剂可有效缩短发酵时间,并能减少堆肥过程的碳、氮损失.施用发酵后蚕沙的小白菜和番茄种子的发芽指数均大于80%,对作物发芽没有抑制作用.施用发酵蚕沙有机肥不仅可提高小白菜产量、营养养分、Vc含量,减少硝酸盐积累量,还可提高土壤pH值,增加土壤速效养分和有机质含量,增强土壤酶活性,其效果优于发酵羊粪有机肥处理. 相似文献
999.
From January 2008 to February 2009, a field experiment was conducted in Rainy Area of West China to understand the effects of nitrogen (N) deposition on the soil respiration in a Bambusa pervariabilis x Dendrocala mopsi plantation. Four treatments were installed, i. e., no N added (control), 5 g N m(-2) a(-1) (low-N), 15 g N m(-2) a(-1) (medium-N), and 30 g N m(-2) a(-1) (high-N), and soil respiration rate was determined by infra-red CO2 analyzer. In the plantation, soil respiration rate had an obvious seasonal change, with the maximum in July and the minimum in January. In control plot, the annual cumulative soil respiration was (389 +/- 34) g m(-2) a(-1). Soil respiration rate had significant positive exponential relationships with soil temperature at 10 cm depth and air temperature, and significant positive linear relationships with soil microbial biomass carbon (MBC) and nitrogen (MBN). Simulated N deposition promoted soil respiration significantly, with significant differences between the low- and medium-N and the control but no significant difference between high-N and the control. In control plot, surface soil (0-20 cm) MBC and MBN were 0.460 and 0.020 mg g(-1), respectively. In N-added plots, both the MBC and the MBN had significant increase. The fine root density in surface soil was 388 g m(-2), which was less affected by simulated N deposition. The soil respiration Q10 value calculated from soil temperature at 10 cm depth and air temperature was 2.66 and 1.87, respectively, and short-term N deposition had lesser effects on the Q10 value. The variation of soil respiration in the plantation was mainly controlled by temperature and soil microbial biomass, and simulated N deposition could increase the CO2 emission via increasing soil microbial biomass. 相似文献
1000.
采用PCR-SSCP、克隆测序等方法,分析600只河西绒山羊GOLA-DRB1基因第2外显子遗传特征、SNPs变异类型,同时分析该基因与山羊流产的关联性.结果表明,河西绒山羊DRB1基因第2外显子上存在26个等位基因,序列比对后发现26个等位基因中存在71个核苷酸变异住点,占分析位点总数的30%.其中转换位点25个,占核苷酸多态位点的35.21%;颠换位点35个,占核苷酸多态位点的49.3%;转换和颠换共存位点9个,占12.68%.山羊流产关联性分析结果表明,在河西绒山羊病例组中DRB1*18、DRB1*23、DRBl*26等位基因频率高于正常对照组(P<0.05),x2值分别为6.31,4.859,6.396,RR值为2.55, 2.72,DRB1*8等位基因频率显著高于正常对照组(P<0.01),x2值为17.618,RR值为3.59;病例组中DRB1*14等住基因频率低于正常对照组(P<0.05),x2值为4.812,RR值为0.65,DRB1*1和DRB1*11显著低于正常对照组(P<0.0l),其中B1的x2值和RR值分别为14.11和0.61,初步推断DRB1*8可能是河西绒山羊流产发病单体型中的遗传易感基因,DRB1*1和DRB1*11可能为其遗传保护基因. 相似文献