全文获取类型
收费全文 | 4783篇 |
免费 | 454篇 |
国内免费 | 357篇 |
出版年
2024年 | 18篇 |
2023年 | 75篇 |
2022年 | 143篇 |
2021年 | 258篇 |
2020年 | 175篇 |
2019年 | 258篇 |
2018年 | 221篇 |
2017年 | 139篇 |
2016年 | 240篇 |
2015年 | 353篇 |
2014年 | 342篇 |
2013年 | 360篇 |
2012年 | 430篇 |
2011年 | 362篇 |
2010年 | 259篇 |
2009年 | 230篇 |
2008年 | 255篇 |
2007年 | 231篇 |
2006年 | 193篇 |
2005年 | 138篇 |
2004年 | 126篇 |
2003年 | 129篇 |
2002年 | 97篇 |
2001年 | 87篇 |
2000年 | 57篇 |
1999年 | 73篇 |
1998年 | 42篇 |
1997年 | 35篇 |
1996年 | 39篇 |
1995年 | 28篇 |
1994年 | 27篇 |
1993年 | 31篇 |
1992年 | 31篇 |
1991年 | 27篇 |
1990年 | 23篇 |
1989年 | 11篇 |
1988年 | 16篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 11篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有5594条查询结果,搜索用时 15 毫秒
901.
Peng-Fei Zheng Zhuang Xiong Cui-ying Liao Xin Zhang Mei Feng Xiao-Zheng Wu Jing Lin Lin-Sheng Lei You-Cheng Zhang Shao-Hua Wang Xue-Tao Xu 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1938
In this paper, bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated for their inhibitory activity against α-glucosidase and α-amylase. All synthesised compounds showed potential α-glucosidase and α-amylase inhibitory activities. Compounds 5 g (IC50: 7.54 ± 1.10 μM), 5e (IC50: 9.00 ± 0.97 μM), and 5 h (IC50: 9.57 ± 0.62 μM) presented strongest inhibitory activities against α-glucosidase, that were ∼ 30 times stronger than acarbose. Compounds 5 g (IC50: 32.18 ± 1.66 µM), 5 h (IC50: 31.47 ± 1.42 µM), and 5 s (IC50: 30.91 ± 0.86 µM) showed strongest inhibitory activities towards α-amylase, ∼ 2.5 times stronger than acarbose. The mechanisms and docking simulation of the compounds were also studied. Compounds 5 g and 5 h exhibited bifunctional inhibitory activity against these two enzymes. Furthermore, compounds showed no toxicity against 3T3-L1 cells and HepG2 cells.
Highlights
- A series of bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated inhibitory activities against α-glucosidase and α-amylase.
- Compound 5g exhibited promising activity (IC50 = 7.54 ± 1.10 μM) against α-glucosidase.
- Compound 5s exhibited promising activity (IC50 = 30.91 ± 0.86 μM) against α-amylase.
- In silico studies were performed to confirm the binding interactions of synthetic compounds with the enzyme active site.
902.
胶原与壳聚糖是2种具有较好生物相容性和一定力学强度的天然高分子,可在肌腱组织工程中用于细胞外基质的构建,但二者单独使用时各有不足.本研究利用二者性能上的互补,在一定的外力场作用下,采用EDC/NHS对2种天然高分子材料进行共价交联,获得具有一定空间取向和力学强度的多孔支架,然后引入细胞黏附因子RGD进行表面修饰,构建了具有较好组织相容性和细胞亲和性及适当降解速率的人工肌腱组织细胞外基质.对基质材料的力学性能、亲水性、体外降解速率等的检测和显微观察,结果显示:所构建的多孔支架材料柔软富有弹性,抗拉强度达:15.0Mpa,相应形变为:7.33%;孔隙率:79.4%;吸水率:772%;保水率:206%;在RPM1640培养液(含10%胎牛血清)和人血清中,3周总降解率分别为4.13%和37.2%,其降解速率可与肌腱修复周期相吻合,RGD修饰后材料对3T3-L1细胞具有较好的亲和性.有望成为理想的人工肌腱组织和人造皮肤细胞外基质,或整形手术的软组织填充材料. 相似文献
903.
脱硫工程菌的构建及其脱硫性能分析 总被引:1,自引:0,他引:1
以专一性脱硫菌德氏假单胞菌Pseudomonas delafieldii R-8为出发菌株, 利用pPR9TT穿梭质粒构建脱硫操纵子表达载体, 转化原始菌培养得到1株多拷贝脱硫基因的脱硫工程菌R-8-1, 并对其脱硫性能进行了研究。结果表明, 在同样的生物催化脱硫反应条件下, 工程菌的脱硫活性达到6.25 mmol DBT/g dry cell/h, 是原始菌的2倍; 柴油的脱硫试验表明, 在12 h内工程菌静息细胞能将柴油硫含量从310.8 mg/L降至100.1 mg/ L, 脱硫率达到68%, 而原始菌为53%。进一步比较了重组质粒pPR-dsz在工程菌株中传代的稳定性, 试验表明pPR-dsz在工程菌株R-8-1中具有良好的遗传稳定性。此研究为生物脱硫提供了1株优良的工程菌株, 并为该技术的应用提供了参考。 相似文献
904.
利用双向指示种(TWINSPAN)分类技术将黄河三角洲湿地草本植被划分为7个群落类型,然后应用双变量主坐标分析(double principal coordinate analysis, DPCoA)法对其进行排序,结果表明:在物种组成上,芦苇+盐地碱蓬群落为芦苇群落和盐地碱蓬+芦苇群落、盐地碱蓬群落、盐地碱蓬+补血草+碱蓬群落、补血草群落的过渡类型,而芦苇+穗状狐尾藻群落与其他群落类型差异较大;黄河三角洲湿地草本植被的分布主要与土壤因子中的土壤盐分、土壤pH等紧密相关,而与土壤全磷、全氮、有机质等养分无显著相关关系。将DPCoA和其他一些常用的植被排序方法进行了比较,相对于主分量分析(PCA)和除趋势对应分析(DCA)而言,DPCoA信息保留量更高,能够将物种组成和类别上较为接近的植物群落聚集在一起,而将差异较大的植物群落在排序图中分散开来,在揭示群落间相互关系以及植被与环境之间关系上可能更为有效。 相似文献
905.
Kemnitzer W Jiang S Zhang H Kasibhatla S Crogan-Grundy C Blais C Attardo G Denis R Lamothe S Gourdeau H Tseng B Drewe J Cai SX 《Bioorganic & medicinal chemistry letters》2008,18(20):5571-5575
As a continuation of our efforts to discover and develop the apoptosis inducing 4-aryl-4H-chromenes as potential anticancer agents, we explored the removal of the chiral center at the 4-position and prepared a series of 4-aryl-2-oxo-2H-chromenes. It was found that, in general, removal of the chiral center and replacement of the 2-amino group with a 2-oxo group were tolerated and 4-aryl-2-oxo-2H-chromenes exhibited SAR similar to 4-aryl-2-amino-4H-chromenes. The 4-aryl-2-oxo-2H-chromenes with a N-methyl pyrrole fused at the 7,8-positions were highly active with compound 2a having an EC(50) value of 13 nM in T47D cells. It was found that an OMe group was preferred at the 7-position. 7-NMe(2), 7-NH(2), 7-Cl and 7,8 fused pyrido analogs all had low potency. These 4-aryl-2-oxo-2H-chromenes are a series of potent apoptosis inducers with potential advantage over the 4-aryl-2-amino-4H-chromenes series via elimination of the chiral center at the 4-position. 相似文献
906.
Ling Q Huang Y Zhou Y Cai Z Xiong B Zhang Y Ma L Wang X Li X Li J Shen J 《Bioorganic & medicinal chemistry》2008,16(15):7399-7409
A novel synthesis of the human leukocyte common antigen-related (LAR) phosphatase inhibitor, illudalic acid, has been achieved by a route more amenable to structure modifications. A series of simpler analogues of illudalic acid was synthesized and evaluated for potency in inhibiting LAR. The structure-activity relationship (SAR) study has shown that the 5-formyl group and the hemi-acetal lactone are crucial for effective inhibition of LAR activity, and are the key pharmacophores of illudalic acid. The fused dimethylcyclopentene ring moiety evidently helps to enhance the potency of illudalic acid against LAR. A preliminary study of the mechanism of action of illudalic acid against LAR was conducted using electrospray ionization mass spectrometry (ESI-MS) and molecular docking techniques. The results are in full agreement with the described mechanism. 相似文献
907.
Kuemmerle J Jiang S Tseng B Kasibhatla S Drewe J Cai SX 《Bioorganic & medicinal chemistry》2008,16(8):4233-4241
We have reported the discovery of gambogic acid (GA) as a potent apoptosis inducer and the identification of transferrin receptor as its molecular target. In order to understand the basic pharmacophore of GA for inducing apoptosis and to discover novel and simplified derivatives as potential anti-cancer agents, we explored the synthesis of caged 2,3,3a,7a-tetrahydro-3,6-methanobenzofuran-7(6H)-ones (4-oxatricyclo[4.3.1.0]decan-2-ones). Three types of 2,3,3a,7a-tetrahydro-3,6-methanobenzofuran-7(6H)-ones based on xanthone, 2-phenylchromene-4-one and benzophenone, were synthesized using a Claisen/Diels-Alder reaction cascade. All the reactions produced the targeted caged compound as well as its neo-isomer. The caged compounds based on xanthone and 2-phenylchromene-4-one were found to maintain the apoptosis inducing and cell growth inhibiting activity of GA, although with less potency. The caged compounds based on benzophenone were found to be inactive. Our study determined the minimum structure of GA for its apoptosis inducing activity, which could lead to the development of simple derivatives as potential anti-cancer drugs. 相似文献
908.
Jian Wu Donghai Zhou Changyan Deng Yuanzhu Xiong Minggang Lei Fenge Li Siwen Jiang Bo Zuo Rong Zheng 《遗传、选种与进化》2008,40(2):227-239
Carbonic anhydrase III (CA3) is an abundant muscle protein characteristic of adult type-1, slow-twitch, muscle fibres. In order to further understand the functions of the porcine CA3 protein in muscle, the temporal and spatial distributions of its gene product were analysed and the association between the presence of specific polymorphisms and carcass traits in the pig was also examined. Real-time PCR revealed that the CA3 mRNA expression showed no differences with age in skeletal muscles from Yorkshire pigs at postnatal day-1, month-2, and month-4. We provide the first evidence that CA3 is differentially expressed in the skeletal muscle of Yorkshire and Meishan pig breeds. In addition, the whole pig genomic DNA sequence of CA3 was investigated and shown to contain seven exons and six introns. Comparative sequencing of the gene from three pig breeds revealed the existence of microsatellite SJ160 in intron 5 and microsatellite SJ158 and a novel microsatellite marker that includes a tandem repeat of (TC)n in intron 4. We also determined the allele number and frequencies of the three loci in seven pig breeds and found that they are low polymorphic microsatellite markers. Statistical analysis showed that the CA3 microsatellite polymorphism was associated with dressing percentage, internal fat rate, carcass length, rib number and backfat thickness in the pig. 相似文献
909.
910.
杆状病毒转导不同哺乳动物骨髓来源间充质干细胞 总被引:1,自引:0,他引:1
杆状病毒作为一种新型基因载体,若能有效转导不同哺乳动物骨髓来源间充质干细胞(bone marrow-derived mesenchymal stem cells, BMSCs),将会成为干细胞基因修饰研究领域中更理想的一种基因载体.本文探讨了重组杆状病毒(BacV-CMV-EGFP)对不同哺乳动物BMSCs的转导效率.体外原代培养小鼠、大鼠、猪、恒河猴及人的BMSCs.用培养3代以上的哺乳动物BMSCs进行病毒转导实验,转导2d后用倒置荧光显微镜观察绿色荧光蛋白在不同哺乳动物BMSCs中的表达,并用流式细胞仪检测重组杆状病毒对不同哺乳动物BMSCs的转导效率.结果显示:原代培养的小鼠、大鼠、猪、恒河猴及人的BMSCs于体外传代3次以上后,细胞呈现较均一的梭形,漩涡状生长;倒置荧光显微镜观察显示,与小鼠、大鼠、猪的BMSCs相比,恒河猴及人有更多BMSCs表达绿色荧光蛋白,且荧光强度较强;杆状病毒对小鼠、大鼠、猪、恒河猴及人的BMSCs的转导效率分别为(21.21±3.02)%、(22.51±4.48)%、(39.13±5.79)%、(71.16±5.36)%及(70.67±3.74)%.上述结果表明,重组杆状病毒对不同哺乳动物BMSCs的转导效率不同,对恒河猴及人的BMSCs转导效率较高,说明重组杆状病毒可作为人或灵长类动物BMSCs基因修饰研究领域中更理想的基因载体. 相似文献