全文获取类型
收费全文 | 11832篇 |
免费 | 1035篇 |
国内免费 | 200篇 |
出版年
2023年 | 49篇 |
2022年 | 139篇 |
2021年 | 246篇 |
2020年 | 166篇 |
2019年 | 223篇 |
2018年 | 323篇 |
2017年 | 227篇 |
2016年 | 397篇 |
2015年 | 627篇 |
2014年 | 720篇 |
2013年 | 715篇 |
2012年 | 953篇 |
2011年 | 884篇 |
2010年 | 585篇 |
2009年 | 530篇 |
2008年 | 692篇 |
2007年 | 657篇 |
2006年 | 611篇 |
2005年 | 580篇 |
2004年 | 549篇 |
2003年 | 495篇 |
2002年 | 419篇 |
2001年 | 367篇 |
2000年 | 286篇 |
1999年 | 257篇 |
1998年 | 97篇 |
1997年 | 98篇 |
1996年 | 77篇 |
1995年 | 75篇 |
1994年 | 53篇 |
1993年 | 36篇 |
1992年 | 92篇 |
1991年 | 98篇 |
1990年 | 64篇 |
1989年 | 64篇 |
1988年 | 58篇 |
1987年 | 53篇 |
1986年 | 42篇 |
1985年 | 47篇 |
1984年 | 38篇 |
1982年 | 27篇 |
1981年 | 23篇 |
1980年 | 23篇 |
1979年 | 25篇 |
1978年 | 23篇 |
1977年 | 25篇 |
1976年 | 29篇 |
1974年 | 25篇 |
1973年 | 23篇 |
1971年 | 25篇 |
排序方式: 共有10000条查询结果,搜索用时 109 毫秒
921.
922.
Jehun Choi Sung Jin Bae Young Mi Ha Jae Kyung No Eun Kyeong Lee Jun Sik Lee Suhee Song Hyojin Lee Hongsuk Suh Byung Pal Yu Hae Young Chung 《Bioorganic & medicinal chemistry letters》2010,20(16):4882-4884
In searching for new agents with a depigmenting effect, we synthesized a derivative of resveratrol, 5-(6-hydroxy-2-naphthyl)-1,2,3-benzenetriol (5HNB) with a potent tyrosinase inhibitory activity. 5HNB inhibited mushroom tyrosinase with an IC50 value of 2.95 μM, which is more potent than the well-known anti-tyrosinase activity of kojic acid (IC50 = 38.24). The results of the enzymatic inhibition kinetics by Lineweaver–Burk analysis indicated 5HNB inhibits tyrosinase non-competitively when l-tyrosine was used as the substrate. Based on the strong inhibitory action of 5HNB, it is expected that 5HNB can suppress melanin production in which tyrosinase plays the essential role. Our expectation was confirmed by the experimentations with B16 melanoma cells in which 5HNB inhibited melanin production. We propose that 5HNB might have skin-whitening effects as well as therapeutic potential for treating skin pigmentation disorders. 相似文献
923.
Kuei-Min Chung Jai-Hong Cheng Ching-Shu Suen Chih-Hsiang Huang Cheng-Han Tsai Li-Hao Huang Yi-Rong Chen Andrew H-J Wang Weir-Torn Jiaang Ming-Jing Hwang Xin Chen 《Protein science : a publication of the Protein Society》2010,19(9):1627-1638
Dipeptidyl peptidase IV (DPP‐IV) is a drug target in the treatment of human type II diabetes. It is a type II membrane protein with a single transmembrane domain (TMD) anchoring the extracellular catalytic domain to the membrane. DPP‐IV is active as a dimer, with two dimer interacting surfaces located extracellularly. In this study, we demonstrate that the TM of DPP‐IV promotes DPP‐IV dimerization and rescues monomeric DPP‐IV mutants into partial dimers, which is specific and irreplaceable by TMs of other type II membrane proteins. By bioluminescence resonance energy transfer (BRET) and peptide electrophoresis, we found that the TM domain of DPP‐IV is dimerized in mammalian cells and in vitro. The TM dimer interaction is very stable, based on our results with TM site‐directed mutagenesis. None of the mutations, including the introduction of two prolines, resulted in their complete disruption to monomers. However, these TM proline mutations result in a significant reduction of DPP‐IV enzymatic activity, comparable to what is found with mutations near the active site. A systematic analysis of TM structures deposited in the Protein Data Bank showed that prolines in the TM generally produce much bigger kinking angles than occur in nonproline‐containing TMs. Thus, the proline‐dependent reduction in enzyme activity may result from propagated conformational changes from the TM to the extracellular active site. Our results demonstrate that TM dimerization and conformation contribute significantly to the structure and activity of DPP‐IV. Optimal enzymatic activity of DPP‐IV requires an optimal interaction of all three dimer interfaces, including its TM. 相似文献
924.
Stéphanie Blanchard Anthony D. William Angeline C.-H. Lee Anders Poulsen Ee Ling Teo Weiping Deng Noah Tu Evelyn Tan Kay Lin Goh Wai Chung Ong Chee Pang Ng Kee Chuan Goh Zahid Bonday Eric T. Sun 《Bioorganic & medicinal chemistry letters》2010,20(8):2443-2447
A series of alkenyl indazoles were synthesized and evaluated in Aurora kinase enzyme assays. Several promising leads were optimized for selectivity towards Aurora B. Excellent binding affinity and good selectivity were achieved with optimized compounds in isolated Aurora subfamily assays. 相似文献
925.
Kyung Sook Chung So Yeon Yoo Seong Jeon Yoo Jong Seob Lee Ji Hoon Ahn 《Plant signaling & behavior》2010,5(9):1102-1104
Transition to the flowering stage is precisely controlled by a few classes of regulatory molecules. BROTHER OF FT AND TFL1 (BFT) is a member of FLOWERING LOCUS T (FT)/TERMINAL FLOWER 1 (TFL1) family, an important class of flower development regulators with unidentified biochemical function. BFT has a TFL1-like activity and plays a role in axillary inflorescence development. To elucidate the expression pattern of BFT, we analyzed the subcellular localization and conditional expression of BFT in this study. We generated 35S::BFT:GFP plants to investigate the subcellular localization of BFT protein. 35S::BFT:GFP plants showed late flowering, similarly as did 35S::BFT plants. BFT:GFP fusion protein was localized in the nucleus and the plasma membrane, which was different from the localization pattern of FT and TFL1. BFT expression was induced by abiotic stress conditions. ABA, drought, and osmotic stress treatments induced BFT expression, whereas cold, salt, and heat stress conditions did not, suggesting that BFT plays a role in regulating flowering time and inflorescence structure under drought conditions. The induction pattern of BFT was different from those of other FT/TFL1 family genes. Our studies indicated that BFT showed a distinct expression pattern from its homologous genes during the vegetative growth in Arabidopsis.Key words: flowering time, flowering locus T, terminal flower 1, brother of FT and TFL1, abiotic stress, subcellullar localizationThe FLOWERING LOCUS T (FT)/TERMINAL FLOWER 1 (TFL1) family is a small gene family whose members play a pivotal role in flower development in Arabidopsis. The family includes FT, TFL1, TWIN SISTER OF FT (TSF), Arabidopsis thaliana CENTRORADIALIS homologue (ATC), MOTHER OF FT AND TFL1 (MFT) and BROTHER OF FT AND TFL1 (BFT).3,5,6,9,15,17 FT is a floral promoter that integrates signal inputs from various pathways that regulate flowering time in Arabidopsis.5,6 TFL1 plays an antagonistic role to that of FT, functioning as a floral inhibitor. Unlike FT, TFL1 also plays an important role in controlling plant architecture by regulating the expression of LEAFY (LFY) and APETALA1 (AP1), two important floral meristem identity genes in the shoot apical meristem (SAM).3,7 TSF regulates flowering by a mechanism similar to that of FT, although a lesion in TSF does not have an apparent effect on the determination of flowering time. MFT has a weak FT-like activity.17 ATC acts as a floral repressor, and its role is similar to that of TFL1.9 Finally, BFT has a TFL1-like activity, in spite of its amino acid homology to FT,2,4,16 and functions redundantly with TFL1 in inflorescence meristem development in Arabidopsis.16 Although genetic studies elucidated an intricate role of the FT/TFL1 family genes, not much is known about the expression pattern of the remaining members except FT and TFL1. Here, we report that BFT expression showed a distinct pattern from its homologous genes during the vegetative phase. BFT:GFP fusion protein was detected in the nucleus and the plasma membrane. BFT expression was induced by abiotic stress conditions, distinct from other FT/TFL1 family genes, raising the possibility that BFT plays a role in regulating flowering time and inflorescence structure under drought conditions. 相似文献
926.
Fanconi anemia (FA) patients are specifically defective in the repair of interstrand DNA crosslinks (ICLs), a complex process involving at least 13 FA proteins and other repair/checkpoint proteins. Of the 13 FA proteins, FANCD1/BRCA2, FANCD2, and FANCJ were previously found to be functionally conserved in C. elegans. We have also identified C. elegans homologs of FANCM and FANCI, and determined their epistatic relationships with homologs of FANCD2, checkpoint proteins, and RAD51 upon DNA crosslinking. The counterparts of FANCM, FANCI, and three checkpoint proteins (RPA, ATR and CHK1) are required for focus formation and ubiquitination associated with FANCD2 in C. elegans. However, C. elegans FANCM affects neither RPA focus formation nor CHK1 phosphorylation induced by ICLs, unlike the reported role of human FANCM, which influences ATR-CHK1 signaling at stalled replication forks. Although focus formation by both FANCD2 and RAD51 requires ATR-CHK1 signaling, FANCD2 and RAD51 acted independently in the formation of their respective foci. Thus, the FANCD2 activation pathway involving FANCM, FANCI, and the checkpoint proteins is conserved in C. elegans but with distinct differences. 相似文献
927.
In-Seok Oh Ji-Chul Lee Myung-shin Lee Jun-ho Chung Dong-Myung Kim 《Bioprocess and biosystems engineering》2010,33(1):127-132
Botulinum neurotoxin serotype B (BoNT/B)-specific Fab was expressed in a cell-free protein synthesis system derived from an
E. coli extract. The cell-free synthesized antibody fragment was found to be effective in neutralizing the toxicity of BoNT/B in
animal studies. Expression of functional Fab required an appropriately controlled and stably maintained redox potential. Under
an optimized redox condition, the cell extract, whose disulfide reducing activity had been exhausted, could generate bio-functional
Fab molecules. Use of a cell extract enriched with molecular chaperones (GroEL/ES) and disulfide bond isomerases were effective
in obtaining larger quantities of functional Fab. Under the optimized reaction conditions, approximately 30 μg of functional
Fab was obtained after purification from 1 mL reaction mixture. 相似文献
928.
Gastric juice is the most proximal fluid surrounding the stomach tissue. The analysis of gastric juice protein contents will thus be able to accurately reflect the pathophysiology of the stomach. This biological fluid is also a potential reservoir of secreted biomarkers in higher concentration as compared to the serum. Unlike the rest of the gastrointestinal fluids, there were very few studies reported on gastric juice proteome. To date, the proteins that routinely populate this biofluid are largely unknown. This is partly due to the technical difficulties in processing a sample that contains a collection of other gastrointestinal fluids, especially saliva. In this study, we attempt to profile the protein components of the gastric fluids from chronic gastritis patients using a direct shotgun proteomics approach. These data represent the first report of the proteome of human gastric juice with gastritis background. 相似文献
929.
Zhao WG Chung JW Cho YI Rha WH Lee GA Ma KH Han SH Bang KH Park CB Kim SM Park YJ 《Comptes rendus biologies》2010,333(11-12):793-800
This study was conducted to assess the genetic diversity and population structure of 139 Lycium chinense accessions using 18 simple sequence repeat (SSR) markers. In total, 108 alleles were detected. The number of alleles per marker locus ranged from two to 17, with an average of six. The gene diversity and polymorphism information content value averaged 0.3792 and 0.3296, with ranges of 0.0793 to 0.8023 and 0.0775 to 0.7734, respectively. The average heterozygosity was 0.4394. The model-based structure analysis revealed the presence of three subpopulations, which was consistent with clustering based on genetic distance. An AMOVA analysis showed that the between-population component of genetic variance was less than 15.3%, in contrast to 84.7% for the within-population component. The overall FST value was 0.1178, indicating a moderate differentiation among groups. The results could be used for future L. chinense allele mining, association mapping, gene cloning, germplasm conservation, and designing effective breeding programs. 相似文献
930.
The objective of this study was to compare thermal sensitivity of recipient ooplasm and donor nucleus from Holstein and Taiwan native yellow (TY) cows. Oocytes and cumulus cells from each breed were incubated at 43 °C (heat shock) or 38.5 °C (control) for 1 h prior to nucleus transplantation. Reconstructed embryos cloned by transfer of non-heated Holstein donor cells to heat-shocked Holstein ooplasm (Ho+-Hd−) had a lower (P < 0.05) blastocyst rate than those cloned from non-heated Holstein ooplasm receiving heated (Ho−-Hd+) or non-heated (Ho−-Hd−) Holstein donor cells (11.3 vs. 34.3 or 36.8%). Heat-shocked donor cells from either Holstein or TY cows did not significantly affect blastocyst rates of reconstructed embryos produced from Holstein ooplasm (30.6-32.9%). In contrast, blastocyst rates of reconstructed embryos generated with heat-shocked Holstein ooplasm were lower (P < 0.05) than that with heat-shocked TY ooplasm (11.2 vs 45.2%). Without heat shock, embryos reconstructed by transferring donor cells to ooplasm of Holstein or TY cows had similar (P > 0.05) blastocyst rates (28.9-33.3%). Transplantation of reconstructed embryos (n = 30) to recipients (n = 23) resulted in three live calves, derived from embryos cloned with TY ooplasm and donor nuclei from either Holstein (n = 2) or TY cows (n = 1). In conclusion, ooplasm of TY cattle was more resistant to heat stress than that derived from Holsteins; therefore, ooplasm may be a major determinant for thermal sensitivity in bovine oocytes and embryos. 相似文献