全文获取类型
收费全文 | 311篇 |
免费 | 41篇 |
国内免费 | 4篇 |
专业分类
356篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 10篇 |
2020年 | 15篇 |
2019年 | 19篇 |
2018年 | 16篇 |
2017年 | 11篇 |
2016年 | 14篇 |
2015年 | 19篇 |
2014年 | 25篇 |
2013年 | 21篇 |
2012年 | 25篇 |
2011年 | 15篇 |
2010年 | 12篇 |
2009年 | 15篇 |
2008年 | 13篇 |
2007年 | 24篇 |
2006年 | 18篇 |
2005年 | 17篇 |
2004年 | 12篇 |
2003年 | 11篇 |
2002年 | 4篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1989年 | 2篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1977年 | 2篇 |
1974年 | 1篇 |
排序方式: 共有356条查询结果,搜索用时 0 毫秒
131.
132.
Lorena Infante Lara Alexis Sledge Amine Laradji Cosmas O. Okoro Neil Osheroff 《Bioorganic & medicinal chemistry letters》2017,27(3):586-589
A number of topoisomerase II-targeted anticancer drugs, including amsacrine, utilize an acridine or related aromatic core as a scaffold. Therefore, to further explore the potential of acridine-related compounds to act as topoisomerase II poisons, we synthesized a series of novel trifluoromethylated 9-amino-3,4-dihydroacridin-1(2H)-one derivatives and examined their ability to enhance DNA cleavage mediated by human topoisomerase IIα. Derivatives containing a H, Cl, F, and Br at C7 enhanced enzyme-mediated double-stranded DNA cleavage ~5.5- to 8.5-fold over baseline, but were less potent than amsacrine. The inclusion of an amino group at C9 was critical for activity. The compounds lost their activity against topoisomerase IIα in the presence of a reducing agent, displayed no activity against the catalytic core of topoisomerase IIα, and inhibited DNA cleavage when incubated with the enzyme prior to the addition of DNA. These findings strongly suggest that the compounds act as covalent, rather than interfacial, topoisomerase II poisons. 相似文献
133.
Fang X Ye L Timani KA Li S Zen Y Zhao M Zheng H Wu Z 《Journal of biochemistry and molecular biology》2005,38(4):381-385
Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a novel coronavirus (CoV) that was identified and molecularly characterized in 2003. Previous studies on various coronaviruses indicate that protein-protein interactions amongst various coronavirus proteins are critical for viral assembly and morphogenesis. It is necessary to elucidate the molecular mechanism of SARS-CoV replication and rationalize the anti-SARS therapeutic intervention. In this study, we employed an in vitro GST pull-down assay to investigate the interaction between the membrane (M) and the nucleocapsid (N) proteins. Our results show that the interaction between the M and N proteins does take place in vitro. Moreover, we provide an evidence that 12 amino acids domain (194-205) in the M protein is responsible for binding to N protein. Our work will help shed light on the molecular mechanism of the virus assembly and provide valuable information pertaining to rationalization of future anti-viral strategies. 相似文献
134.
Three recent reports (Baoxiu Qi et al., Amine Abbadi et al. and Anthony J. Kinney et al.) describe the production of very long-chain polyunsaturated fatty acids in transgenic plants. This might lead to a sustainable source of these valuable fatty acids for use in human food and animal feed. At present they are mainly available via consumption of fish, which is a limited and endangered resource. 相似文献
135.
Insights into human Lck SH3 domain binding specificity: different binding modes of artificial and native ligands 总被引:1,自引:0,他引:1
Tran T Hoffmann S Wiesehan K Jonas E Luge C Aladag A Willbold D 《Biochemistry》2005,44(45):15042-15052
We analyzed the ligand binding specificity of the lymphocyte specific kinase (Lck) SH3 domain. We identified artificial Lck SH3 ligands using phage display. In addition, we analyzed Lck SH3 binding sites within known natural Lck SH3 binding proteins using an Lck specific binding assay on membrane-immobilized synthetic peptides. On one hand, from the phage-selected peptides, representing mostly special class I' ligands, a well-defined consensus sequence was obtained. Interestingly, a histidine outside the central polyproline motif contributes significantly to Lck SH3 binding affinity and specificity. On the other hand, we confirmed previously mapped Lck SH3 binding sites in ADAM15, HS1, SLP76, and NS5A, and identified putative Lck SH3 binding sites of Sam68, FasL, c-Cbl, and Cbl-b. Without exception, the comparatively diverse Lck SH3 binding sites of all analyzed natural Lck SH3 binding proteins emerged as class II proteins. Possible explanations for the observed variations between artificial and native ligands-which are not due to significant K(D) value differences as shown by calculating Lck SH3 affinities of artificial peptide PD1-Y(-3)R as well as for peptides comprising putative Lck SH3 binding sites of NS5A, Sos, and Sam68-are discussed. Our data suggest that phage display, a popular tool for determining SH3 binding specificity, must-at least in the case of Lck-not irrevocably mirror physiologically relevant protein-ligand interactions. 相似文献
136.
Isolation and Characterization of Clostridium butyricum DSM 5431 Mutants with Increased Resistance to 1,3-Propanediol and Altered Production of Acids 总被引:6,自引:0,他引:6 下载免费PDF全文
S. Abbad-Andaloussi C. Manginot-Durr J. Amine E. Petitdemange H. Petitdemange 《Applied microbiology》1995,61(12):4413-4417
Clostridium butyricum mutants were isolated from the parent strain DSM 5431 after mutagenesis with N-methyl-N(prm1)-nitro-N-nitrosoguanidine and two selection procedures: osmotic pressure and the proton suicide method. Isolated mutants were more resistant to glycerol and to 1,3-propanediol (1,3-PD) than was the wild type, and they produced more biomass. In batch culture on 62 g of glycerol per liter, the wild type produced more acetic acid than butyrate, with an acetate/butyrate ratio of 5.0, whereas the mutants produced almost the same quantities of both acids or more butyrate than acetate with acetate/butyrate ratios from 0.6 to 1.1. The total acid formation was higher in the wild-type strain. Results of analysis of key metabolic enzymatic activities were in accordance with the pattern of fermentation product formation: either the butyrate kinase activity increased or the acetate kinase activity decreased in cell extracts of the mutants. A decreased level of the hydrogenase and NADH-ferredoxin activities concomitant with an increase in ferredoxin-NAD(sup+) reductase activities supports the conclusion that the maximum percentage of NADH available and used for the formation of 1,3-PD was higher for the mutants (97 to 100%) than for the wild type (70%). In fed-batch culture, at the end of the fermentation (72 h for the wild-type strain and 80 to 85 h for the mutants), 44% more glycerol was consumed and 50% more 1,3-PD was produced by the mutants than by the wild-type strain. 相似文献
137.
Michael Hahn Svetlana Borisova Joseph D. Schrag Daniel C. Tessier André Zapun Rosanne Tom Amine A. Kamen John J.M. Bergeron David Y. Thomas Miroslaw Cygler 《Journal of structural biology》1998,123(3):260-264
Calnexin is a molecular chaperone that facilitates folding of glycoproteins in the endoplasmic reticulum (ER). The cloned lumenal domain of canine calnexin, cnxΔTMC, retains its biological activity without the transmembrane and cytosolic region. For the purpose of structure determination we generated a crystallizable core by mild proteolysis and identified its termini by N-terminal sequencing and molecular mass determination. A truncated gene was cloned accordingly. Its product, cnxΔN25C15, was purified to apparent homogeneity and crystallized. This truncated variant remains biologically active as shown by its binding to monoglucosylated oligosaccharides and functional interaction with ERp57. A heavy atom derivative was identified. 相似文献
138.
The last 10 years have seen a rapid expansion in the use of viral gene transfer vectors, with approved therapies and late stage clinical trials underway for the treatment of genetic disorders, and multiple forms of cancer, as well as prevention of infectious diseases through vaccination. With this increased interest and widespread adoption of viral vectors by clinicians and biopharmaceutical industries, there is an imperative to engineer safer and more efficacious vectors, and develop robust, scalable and cost‐effective production platforms for industrialization. This review will focus on major innovations in viral vector design and production systems for three of the most widely used viral vectors: Adenovirus, Adeno‐Associated Virus, and Lentivirus. 相似文献
139.
S Jahan S Singh A Srivastava V Kumar D Kumar A Pandey CS Rajpurohit AR Purohit VK Khanna AB Pant 《Molecular neurobiology》2018,55(4):2828-2839
140.
Chemometric Tools to Highlight the Variability of the Chemical Composition and Yield of Lebanese Origanum syriacum L. Essential Oil 下载免费PDF全文
Raviella Zgheib Sylvain Chaillou Naim Ouaini Amine Kassouf Douglas Rutledge Desiree El Azzi Marc El Beyrouthy 《化学与生物多样性》2016,13(10):1326-1347
This study deals with the variation in the yield and composition of Lebanese Origanum syriacum L. essential oil (EO) according to harvesting time, drying methods used, and geographical location. Plant material was harvested twice a month all over 2013 and 2014 from Qartaba and Achkout located at high altitude and from Byblos at low altitude. EOs of the aerial parts were obtained by hydrodistillation. The highest yields were obtained at full flowering stage and slightly reduced after flowering. The GC/MS analysis revealed the presence of 50 components representing 90.49 – 99.82%, 88.79 – 100%, and 95.28 – 100% of the total oil extracted from plants harvested from Qartaba, Achkout, and Byblos, respectively. The major components in the oils were: carvacrol (2.1 – 79.8%), thymol (0.3 – 83.7%), p‐cymene (2.8 – 43.8%), thymoquinone (0.4 – 27.7%), γ‐terpinene (0.4 – 10.0%), octan‐3‐ol (0.3 – 4.9%), caryophyllene oxide (0.2 – 4.7%), oct‐1‐en‐3‐ol (0.3 – 3.7%), β‐caryophyllene (0.7 – 3.2%), cis‐sabinene hydrate (0.1 – 2.8%), terpinen‐4‐ol (0.1 – 2.8%), and α‐terpinene (0.2 – 2.2%). Independent components analysis (ICA) revealed that two groups were discriminated, reflecting compositional differences in the EOs profiles of the Lebanese oregano samples: O. syriacum grown in Qartaba and Achkout belongs to carvacrol chemotype, while O. syriacum grown in Byblos belongs to thymol chemotype. The flowering phase was the most productive period in terms of yield, bringing marked changes in the EO composition by increasing the amounts of carvacrol or thymol, and decreasing those of thymoquinone and p‐cymene. 相似文献