全文获取类型
收费全文 | 5797篇 |
免费 | 564篇 |
国内免费 | 858篇 |
出版年
2024年 | 19篇 |
2023年 | 87篇 |
2022年 | 241篇 |
2021年 | 309篇 |
2020年 | 226篇 |
2019年 | 253篇 |
2018年 | 218篇 |
2017年 | 194篇 |
2016年 | 230篇 |
2015年 | 362篇 |
2014年 | 426篇 |
2013年 | 484篇 |
2012年 | 585篇 |
2011年 | 491篇 |
2010年 | 342篇 |
2009年 | 341篇 |
2008年 | 371篇 |
2007年 | 329篇 |
2006年 | 258篇 |
2005年 | 279篇 |
2004年 | 226篇 |
2003年 | 209篇 |
2002年 | 170篇 |
2001年 | 106篇 |
2000年 | 82篇 |
1999年 | 78篇 |
1998年 | 93篇 |
1997年 | 47篇 |
1996年 | 29篇 |
1995年 | 26篇 |
1994年 | 23篇 |
1993年 | 13篇 |
1992年 | 18篇 |
1991年 | 14篇 |
1990年 | 7篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 8篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1973年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有7219条查询结果,搜索用时 17 毫秒
891.
Knockdown of damage-specific DNA binding protein 1 (DDB1) enhances the HBx-siRNA-mediated inhibition of HBV replication 总被引:3,自引:0,他引:3
Kai-Fu Tang Jing Xie Min Chen Qi Liu Xi-Yuan Zhou Weiqun Zeng Ai-Long Huang Guo-qing Zuo Yan Wang Rong Xiang Hong Ren 《Biologicals》2008,36(3):177-183
Recent studies have demonstrated that the effect of inhibition of HBV replication can be achieved by RNA interference (RNAi) at both the cellular and organismal levels. However, HBV replication cannot be completely inhibited by this method. To completely inhibit HBV replication, new strategies for improving the inhibition efficacy of HBV-specific siRNAs are needed. In this study, we demonstrated that knockdown of damage-specific DNA binding protein 1(DDB1), a protein involved in nucleotide-excision repair and HBV replication, significantly enhanced the HBx-siRNA-mediated inhibition of HBV replication. Although knockdown of DDB1 may be toxic to normal liver cells, our results indeed suggest a new direction to enhance the efficacy of HBV-siRNA-mediated inhibition of HBV replication. 相似文献
892.
Skp2 regulates G2/M progression in a p53-dependent manner 总被引:1,自引:0,他引:1
Targeted proteasomal degradation mediated by E3 ubiquitin ligases controls cell cycle progression, and alterations in their activities likely contribute to malignant cell proliferation. S phase kinase-associated protein 2 (Skp2) is the F-box component of an E3 ubiquitin ligase complex that targets p27Kip1 and cyclin E1 to the proteasome. In human melanoma, Skp2 is highly expressed, regulated by mutant B-RAF, and required for cell growth. We show that Skp2 depletion in melanoma cells resulted in a tetraploid cell cycle arrest. Surprisingly, co-knockdown of p27Kip1 or cyclin E1 failed to prevent the tetraploid arrest induced by Skp2 knockdown. Enhanced Aurora A phosphorylation and repression of G2/M regulators cyclin B1, cyclin-dependent kinase 1, and cyclin A indicated a G2/early M phase arrest in Skp2-depleted cells. Furthermore, expression of nuclear localized cyclin B1 prevented tetraploid accumulation after Skp2 knockdown. The p53 status is most frequently wild type in melanoma, and the tetraploid arrest and down-regulation of G2/M regulatory genes were strongly dependent on wild-type p53 expression. In mutant p53 melanoma lines, Skp2 depletion did not induce cell cycle arrest despite up-regulation of p27Kip1. These data indicate that elevated Skp2 expression may overcome p53-dependent cell cycle checkpoints in melanoma cells and highlight Skp2 actions that are independent of p27Kip1 degradation. 相似文献
893.
894.
895.
Yang ZH Zeng R Yang G Wang Y Li LZ Lv ZS Yao M Lai B 《Journal of industrial microbiology & biotechnology》2008,35(9):1047-1051
As an important organic compound, chiral alcohols are the key chiral building blocks to many single enantiomer pharmaceuticals. Asymmetric reduction of the corresponding prochiral ketones to produce the chiral alcohols by biocatalysis is one of the most promising routes. Asymmetric reduction of different kinds of non-natural prochiral ketones catalyzed by various plants tissue was studied in this work. Acetophenone, 4'-chloroacetophenone and ethyl 4-chloroacetoacetate were chosen as the model substrates for simple ketone, halogen-containing aromatic ketone and beta-ketoesters, respectively. Apple (Malus pumila), carrot (Daucus carota), cucumber (Cucumis sativus), onion (Allium cepa), potato (Soanum tuberosum), radish (Raphanus sativus) and sweet potato (Ipomoea batatas) were chosen as the biocatalysts. It was found that these kinds of prochiral ketoness could be reduced by these plants tissue with high enantioselectivity. Both R- and S-form configuration chiral alcohols could be obtained. The e.e. and chemical yield could reach about 98 and 80% respectively for acetophenone and 4'-chloroacetophenone reduction reaction with favorable plant tissue. And the e.e. and yield for ethyl 4-chloroacetoacetate reduction reaction was about 91 and 45% respectively. 相似文献
896.
Zha Renming Ling Yinghua Yang Zhenglin Zhao Fangming Zhong Bingqiang Xie Rong Sang Xianchun He Guanghua 《Molecular breeding : new strategies in plant improvement》2008,22(3):467-476
One hundred and fifty-one rice hybrids produced in two sets of half-dialell crosses and their parents (13 cytoplasmic male
sterile lines and 19 restorers) were used to predict the F1 performances of seven yield traits through the parental genetic distances (GD) based on SSR markers. The positive loci (PL)
and effect-increasing loci (IL), which were screened from SSR polymorphic loci by the F1 traits of 32 parents, together with total loci (TL), were utilized to estimate parental GD and the models were found to predict
the traits of hybrids derived from different parents, fixed parents, and different environments, respectively. The results
were as follows: (1) 550 polymorphic loci were detected from 174 SSR markers: a dendrogram based on these loci could separate
all the sterile and restorer lines used in the present study, which indicated that parental genetic diversity of F1 was large; (2) the correlations between F1 traits and parental GDs based on IL ranged from 0.61 to 0.87 with a mean of 0.76, and they were higher than those on TL or
on PL; (3) predictions based on IL for F1 traits (except grain weight per plant) derived from different environments were ideal, but worse for F1 traits derived from different parents; and (4) IL was more effective than TL and PL in predicting traits of F1 with fixed parents, and predictions for fixed restorer combinations were more effective than those for fixed sterile line
combinations. These results should facilitate molecular prediction for hybrid yield and other traits by means of both elite
sterile and restorer lines. 相似文献
897.
Wang GF Shang YJ Jiao BH Huang CG 《Journal of enzyme inhibition and medicinal chemistry》2008,23(3):406-410
The purpose of this study was to evaluate the inhibitory effect of renierol, extracted from marine sponge Halicdona.SP., on xanthine oxidase (XO) and its hypouricemic effect in vivo. Renierol and a positive control, allopurinol, were tested for their effects on XO activity by measuring the formation of uric acid and superoxide radical from xanthine. Renierol inhibited XO in a concentration-dependent and competitive manner. IC(50) value was 1.85 microg.ml(-1) through the measuring of uric acid and was 1.36 microg.ml(- 1) through the measuring of superoxide radical. Renierol was found to have an in vivo hypouricemic activity against potassium oxonate-induced hyperuricaemia in mice. After oral administration of renierol at doses of 10, 20 and 30 mg.kg(- 1), there was a significant decrease in the serum urate level (4.08 +/- 0.09 mg.dl(- 1), P < 0.01), (3.47 +/- 0.11 mg.dl(- 1), P < 0.01) and (3.12 +/- 0.08 mg.dl(- 1), P < 0.01), when compared to the hyperuricaemic control (6.74 +/- 0.23 mg.dl(- 1)). Renierol was a potent XO inhibitor with hypouricemic activity in mice. 相似文献
898.
Wang SH Wang SF Xuan W Zeng ZH Jin JY Ma J Tian GR 《Bioorganic & medicinal chemistry》2008,16(7):3596-3601
2-Substituted 3-nitropropanoic acids were designed and synthesized as inhibitors against carboxypeptidase A (CPA). (R)-2-Benzyl- 3-nitropropanoic acid showed a potent inhibition against CPA (K(i)=0.15 microM). X-ray crystallography discloses that the nitro group well mimics the transition state occurred in the hydrolysis catalyzed by CPA, that is, an O,O'-bidentate coordination to the zinc ion and the two respective hydrogen bonds with Glu-270 and Arg-127. Because the nitro group is a planar species, we proposed (R)-2-benzyl-3-nitropropanoic acid as a pseudo-transition-state analog inhibitor against CPA. 相似文献
899.
The purpose of the present study was to evaluate the effects of serum-starvation, contact-inhibition and roscovitine treatments on cell-cycle synchronization at the G0/G1 stage of ear skin fibroblasts isolated from transgenic cloned cattle. The developmental competence of re-cloned embryos was also examined. Our results showed that the proportion of G0/G1 cells from the serum-starved group at 3, 4 or 5 days was significantly higher compared with 1 or 2 days only (91.5, 91.7 and 93.5% versus 90.1 and 88.8%, respectively, p < 0.05); whilst there was no statistical difference among cells at 3, 4 or 5 days. For roscovitine-treated cells, the proportion of G0/G1 cells at 2, 3, 4 or 5 days was significantly higher than those treated for 1 day only (91.1, 90.1, 89.4 and 91.3% versus 86.51%, respectively, p < 0.05). The proportion of contact-inhibited G0/G1 cells rose significantly with treatment time, but was similar at 3, 4 and 5 days (89.4, 90.4, 91.4, 91.6 and 92.1%, respectively, p < 0.05). The efficiency of obtaining G0/G1 phase cells was lower when roscovitine treatment was employed to synchronize the cell cycle compared with the serum-starvation and contact-inhibition methods (89.7 versus 91.1% and 91.0%, p < 0.05). Moreover, obvious differences were observed in the rate of fused couplets and blastocysts (89.88 +/- 2.70 versus 87.40 +/- 5.13; 44.10 +/- 8.62 versus 58.38 +/- 13.28, respectively, p < 0.05), when nuclear transfer embryos were reconstructed using donors cells that had been serum starved or contact inhibited for 3 days. Our data indicate that 3 day treatment is feasible for harvesting sufficient G0/G1 cells to produce re-cloned transgenic bovine embryos, regardless of whether serum-starvation, contact-inhibition or roscovitine treatments are used as the synchronization methods. 相似文献
900.
As a part of our project aimed at developing new agents of potential application in AD, a new series of 2-phenoxy-indan-1-one derivatives which possess alkylamine side chain were designed, synthesized, and evaluated for their inhibitory activity against AChE and BuChE. Most of the compounds were found to inhibit AChE in the nanomolar range. The optimum inhibitor 3g exhibited 34-fold increase in AChE inhibition than donepezil and displayed neuroprotective effect against H(2)O(2)-induced cell death. 相似文献