全文获取类型
收费全文 | 362篇 |
免费 | 16篇 |
国内免费 | 1篇 |
出版年
2024年 | 2篇 |
2023年 | 7篇 |
2022年 | 14篇 |
2021年 | 6篇 |
2020年 | 13篇 |
2019年 | 19篇 |
2018年 | 19篇 |
2017年 | 17篇 |
2016年 | 13篇 |
2015年 | 11篇 |
2014年 | 22篇 |
2013年 | 33篇 |
2012年 | 20篇 |
2011年 | 25篇 |
2010年 | 24篇 |
2009年 | 11篇 |
2008年 | 9篇 |
2007年 | 17篇 |
2006年 | 10篇 |
2005年 | 13篇 |
2004年 | 23篇 |
2003年 | 12篇 |
2002年 | 12篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1996年 | 1篇 |
1990年 | 2篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1982年 | 1篇 |
1980年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有379条查询结果,搜索用时 15 毫秒
1.
2.
Abstract: 5-Hydroxytryptamine3 (5-HT3 ) receptors are the only known monoamine receptors mediating fast excitatory responses in mammalian neurons. Their primary structure as well as their electrophysiological and pharmacological properties show a phylogenetic relation to nicotinic acetylcholine, GABAA , and glycine receptors. As a prototypical member of this gene superfamily, we investigated the membrane topology of functional homomeric 5-HT3 receptors by using epitope tagging of the channel subunits expressed in heterologous systems. Visualization of 5-HT3 receptors in transfected COS-7 cells, either in western blot (molecular mass 61.2 ± 0.8 kDa) or in situ, was performed with previously characterized antibodies recognizing artificial epitopes as well as with anti-fusion protein antibodies directed against a wild-type receptor intracellular domain. The extracellular location of the distal C-terminal tagged domain demonstrates the presence of a fourth transmembrane domain in 5-HT3 serotonin-gated channels. In this region, the significant homology between members of this class of neurotransmitter-gated channels suggests strongly that they have a common transmembrane organization basically different from glutamate-gated and ATP-gated channels. 相似文献
3.
Aysan Etemadi Salar Hemmati Mohammad Shahrivar-Gargari Yasaman Tamaddon Abibiglue Ahad Bavili Maryam Hamzeh-Mivehroud Siavoush Dastmalchi 《化学与生物多样性》2023,20(8):e202300075
Indanone derivatives containing meta/para-substituted aminopropoxy benzyl/benzylidene moieties were designed based on the structures of donepezil and ebselen analogs as the cholinesterase inhibitors. The designed compounds were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were measured. Inhibitory potencies (IC50 values) for the synthesized compounds ranged from 0.12 to 11.92 μM and 0.04 to 24.36 μM against AChE and BChE, respectively. Compound 5 c showed the highest AChE inhibitory potency with IC50 value of 0.12 μM, whereas the highest BChE inhibition was achieved by structure 7 b (IC50=0.04 μM). Structure-activity relationship (SAR) analysis revealed that there is no significant difference between meta and para-substituted derivatives in AChE and BChE inhibition. However, the most potent AChE inhibitor 5 c belongs to meta-substituted compounds, while the most active BChE inhibitor is para-substituted derivative 7 b . The order of enzyme inhibition potency based on the substituted amine group is dimethyl amine>piperidine>morpholine. Compounds containing C=C linkage are more potent AChE inhibitors than the corresponding saturated structures. Molecular docking studies indicated that 5 c interacts with AChE in a very similar way to that observed experimentally for donepezil. The introduced indanone-aminopropoxy benzylidenes could be used in drug-discovery against Alzheimer's disease. 相似文献
4.
Glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides. Isolation and sequence of a peptide containing an essential lysine 总被引:3,自引:0,他引:3
Interaction of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides with pyridoxal 5'-phosphate and sodium borohydride leads to inactivation and modification of two lysine residues per enzyme dimer that are thought to bind glucose 6-phosphate [Milhausen, M., & Levy, H.R. (1975) Eur. J. Biochem. 50, 453-461]. The amino acid sequence surrounding this lysine residue is reported. Following tryptic hydrolysis of the modified enzyme, two peptides, each containing one pyridoxyllysine residue, were purified to homogeneity and subjected to automated Edman degradation. The sequences revealed that one of these, a heptapeptide, was derived from the other, containing 11 amino acids. Supporting evidence for the role of the modified lysine is provided in the following paper [Haghighi, B., & Levy, H.R. (1982) Biochemistry (second paper of three in this issue)]. End-group analysis of the native enzyme revealed that valine is the N-terminal and glycine the C-terminal amino acid and provides support for the identity of the enzyme's two subunits. 相似文献
5.
Omid Haghighi Soheila Davaeifar Hossein Shahbani Zahiri Hadi Maleki Kambiz Akbari Noghabi 《International journal of peptide research and therapeutics》2020,26(2):783-793
Glutamate dehydrogenase (GDH), which is present in most bacteria and eukaryotes’ mitochondria, plays an important role in amino acid metabolism. In g 相似文献
6.
Masoumi Zeinab Haghighi Maryam Jalali Seyed Amir Hossein 《Molecular biology reports》2021,48(5):4233-4245
Molecular Biology Reports - Both extreme usage of water in agriculture i.e., drought and flooding affect physiological and growth aspects of the plant as well as gene expression undertaken in water... 相似文献
7.
Maysam Mansouri Seyed Jafar Mousavy Zahra Ehsaei Shahram Nazarian Mohammad Reza Zali Seyed Mohammad Moazzeni 《Biologicals》2013,41(3):169-175
Enterotoxigenic Escherichia coli (ETEC) is the most common cause of children diarrhea in the world. Adhesion of ETEC to small intestine is an important virulence trait. One of the most prevalent colonization factors (CFs) in human is CFA/I fimbriae and CfaE which is the required binding factor for adhesion of ETEC to intestinal mucosa.We optimized cfaE gene codons according to codon bias of E. coli to achieve a high level of recombinant protein expression. The optimized gene was expressed in E. coli and rCFaE protein was used for mice immunization. Blocking activity of the obtained antibody was examined by microplate agglutination inhibition test. SDS-PAGE analysis indicated that the optimized sequence of cfaE produces a suitable amount of rCFaE in comparison with native gene sequence. This optimized rCFaE protein could induces strong humoral response in mice and the antibody obtained against rCFaE inhibited the adhesion of ETEC to human group A erythrocytes. It is concluded that codon optimization is a useful approach for obtaining large quantities of recombinant rCFaE protein. With regard to the results of hemagglutination inhibition test, codon optimization and increased production of recombinant protein expressed in E. coli did not affect the immunogenicity potential of CFaE. 相似文献
8.
9.
Mozafari Haniyeh Amiri Shayan Mehr Shahram Ejtemaei Momeny Majid Amini-khoei Hossein Bijani Soroush Hosseini Mir-Jamal 《Molecular biology reports》2020,47(8):6143-6153
Molecular Biology Reports - Neuroinflammation and mitochondrial dysfunction are suggested as mechanisms which are implicated in the pathophysiology of depression. Streptozotocin (STZ) is known to... 相似文献
10.
Noelia Blanco Ambrose J. Williams Danming Tang Dejin Zhan Shahram Misaghi Robert F. Kelley Laura C. Simmons 《Biotechnology and bioengineering》2020,117(7):1946-1960
Optimal production of bispecific antibodies (bsAb) requires efficient and tailored co-expression and assembly of two distinct heavy and two distinct light chains. Here, we describe a novel technology to modulate the translational strength of antibody chains via Kozak sequence variants to produce bsAb in a single cell line. In this study, we designed and screened a large Kozak sequence library to identify 10 independent variants that can modulate protein expression levels from approximately 0.2 to 1.3-fold compared with the wild-type sequence in transient transfection. We used a combination of several of these variants, covering a wide range of translational strength, to develop stable single cell Chinese hamster ovary bispecific cell lines and compared the results with those obtained from the wild-type sequence. A significant increase in bispecific antibody assembly with a concomitant reduction in the level of product-related impurities was observed. Our findings suggest that for production of bsAb it can be advantageous to modify translational strength for selected protein chains to improve overall yield and product quality. By extension, tuning of translational strength can also be applied to improving the production of a wide variety of heterologous proteins. 相似文献