全文获取类型
收费全文 | 170篇 |
免费 | 7篇 |
出版年
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 12篇 |
2013年 | 5篇 |
2012年 | 14篇 |
2011年 | 18篇 |
2010年 | 6篇 |
2009年 | 9篇 |
2008年 | 9篇 |
2007年 | 18篇 |
2006年 | 11篇 |
2005年 | 6篇 |
2004年 | 5篇 |
2003年 | 7篇 |
2002年 | 7篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1996年 | 1篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有177条查询结果,搜索用时 15 毫秒
131.
Bajgar J Hajek P Slizova D Krs O Fusek J Kuca K Jun D Bartosova L Blaha V 《Chemico-biological interactions》2007,165(1):14-21
Acetylcholinesterase activity in defined brain regions was determined using biochemical and histochemical methods 30 min after treating rats with sarin, soman or VX (0.5 x LD(50)). Enzyme inhibition was high in the pontomedullar area and frontal cortex, but was low in the basal ganglia. Histochemical and biochemical results correlated well. Determination of the activity in defined brain structures was a more sensitive parameter than determination in whole brain homogenate where the activity was a "mean" of the activities in different structures. The pontomedullar area controls respiration, so that the special sensitivity of acetylcholinesterase to inhibition by nerve agents in this area is important for understanding the mechanism of death caused by nerve agents. Thus, acetylcholinesterase activity is the main parameter investigated in studies searching for target sites following nerve agent poisoning. 相似文献
132.
Molecular cloning and expression of the human and mouse homologues of the Drosophila dachshund gene 总被引:2,自引:0,他引:2
Zbynek Kozmik Peter Pfeffer Jarmila Kralova J. Paces Vaclav Paces Anna Kalousova A. Cvekl 《Development genes and evolution》1999,209(9):537-545
Recent genetic analysis of the Drosophila dachshund (dac) gene has established that dac encodes a novel nuclear protein that is involved in both eye and leg development. In the Drosophila eye, dac expression appears to be controlled by the product of the eyeless/Pax6 gene. In order to analyze the Pax6 pathway in vertebrates we have isolated and characterized the cDNA and genomic clones corresponding to the human and mouse
homologues of Drosophila
dac. A full-length human cDNA encoding dachshund (DACH) encodes the 706 amino acids protein with predicted molecular weight of 73 kDa. A 109 amino acid domain located at the N-terminus
of the DACH showed significant sequence and secondary structure homologies to the ski/sno oncogene products. Northern blot
analysis found human DACH predominantly in adult kidney, heart, and placenta, with less expression detected in the brain,
lung, skeletal muscle and pancreas. A panel of human cell lines was studied and most notably a large proportion of neuroblastomas
expressed DACH mRNA. Mouse Dach encodes a protein of 751 amino acids with predicted molecular weight of 78 kDa that is 95%
identical to the human DACH. RNase protection analysis showed the highest Dach mRNA expression in the adult mouse kidney and
lung, whereas lower expression was detected in the brain and testis. RT/PCR analysis readily detected Dach mRNA in the adult
mouse cornea and retina. Dach mRNA expression in the mouse E11.5 embryo was observed primarily in the fore and hind limbs,
as well as in the somites.
Received: 9 February 1999 / Accepted: 19 April 1999 相似文献
133.
134.
Karla
Gisel Calderon-Gonzlez Ixaura Medina-Medina Lucia Haronikova Lenka Hernychova Ondrej Bonczek Lukas Uhrik Vaclav Hrabal Borivoj Vojtesek Robin Fahraeus Jesús Hernndez-Monge Vanesa Olivares-Illana 《Bioscience reports》2022,42(7)
HDMX and its homologue HDM2 are two essential proteins for the cell; after genotoxic stress, both are phosphorylated near to their RING domain, specifically at serine 403 and 395, respectively. Once phosphorylated, both can bind the p53 mRNA and enhance its translation; however, both recognize p53 protein and provoke its degradation under normal conditions. HDM2 has been well-recognized as an E3 ubiquitin ligase, whereas it has been reported that even with the high similarity between the RING domains of the two homologs, HDMX does not have the E3 ligase activity. Despite this, HDMX is needed for the proper p53 poly-ubiquitination. Phosphorylation at serine 395 changes the conformation of HDM2, helping to explain the switch in its activity, but no information on HDMX has been published. Here, we study the conformation of HDMX and its phospho-mimetic mutant S403D, investigate its E3 ligase activity and dissect its binding with p53. We show that phospho-mutation does not change the conformation of the protein, but HDMX is indeed an E3 ubiquitin ligase in vitro; however, in vivo, no activity was found. We speculated that HDMX is regulated by induced fit, being able to switch activity accordingly to the specific partner as p53 protein, p53 mRNA or HDM2. Our results aim to contribute to the elucidation of the contribution of the HDMX to p53 regulation. 相似文献
135.
136.
Vaclav Veverka Terry Baker Nicholas T. Redpath Bruce Carrington Frederick W. Muskett Richard J. Taylor Alastair D. G. Lawson Alistair J. Henry Mark D. Carr 《The Journal of biological chemistry》2012,287(47):40043-40050
A number of secreted cytokines, such as interleukin-6 (IL-6), are attractive targets for the treatment of inflammatory diseases. We have determined the solution structure of mouse IL-6 to assess the functional significance of apparent differences in the receptor interaction sites (IL-6Rα and gp130) suggested by the fairly low degree of sequence similarity with human IL-6. Structure-based sequence alignment of mouse IL-6 and human IL-6 revealed surprising differences in the conservation of the two distinct gp130 binding sites (IIa and IIIa), which suggests a primacy for site III-mediated interactions in driving initial assembly of the IL-6/IL-6Rα/gp130 ternary complex. This is further supported by a series of direct binding experiments, which clearly demonstrate a high affinity IL-6/IL-6Rα-gp130 interaction via site III but only weak binding via site II. Collectively, our findings suggest a pathway for the evolution of the hexameric, IL-6/IL-6Rα/gp130 signaling complex and strategies for therapeutic targeting. We propose that the signaling complex originally involved specific interactions between IL-6 and IL-6Rα (site I) and between the D1 domain of gp130 and IL-6/IL-6Rα (site III), with the later inclusion of interactions between the D2 and D3 domains of gp130 and IL-6/IL-6Rα (site II) through serendipity. It seems likely that IL-6 signaling benefited from the evolution of a multipurpose, nonspecific protein interaction surface on gp130, now known as the cytokine binding homology region (site II contact surface), which fortuitously contributes to stabilization of the IL-6/IL-6Rα/gp130 signaling complex. 相似文献
137.
Z Kostrouch V Mandys V Felt F Rehák J Beaufort E Holecková 《Physiologia Bohemoslovaca》1984,33(5):399-402
Normal human thyroid cells and cells from patients with Grave's disease were cultured for 5 months (11 passages) in vitro. Both normal and diseased thyreocytes, similar in morphology, proliferated actively and responded to thyrotropin stimulation by cytoplasmic arborization of a part of the population. Slight inhibition of mitotic activity was present under the influence of thyrotropin. 相似文献
138.
Using cytochemical methods, the authors tested enzymatic reactions in L-As and L-C3 cells. They found that esterase activity in particular, but also several other enzyme activities, were higher in L-C3 cells than in L-As cells. This furnished further evidence of the raised metabolic activity of the cold-resistant cell subline L-C3 compared with the L-As line. 相似文献
139.
Tomas Wald Adriana Osickova Miroslav Sulc Oldrich Benada Alena Semeradtova Lenka Rezabkova Vaclav Veverka Lucie Bednarova Jan Maly Pavel Macek Peter Sebo Ivan Slaby Jiri Vondrasek Radim Osicka 《The Journal of biological chemistry》2013,288(31):22333-22345
Tooth enamel, the hardest tissue in the body, is formed by the evolutionarily highly conserved biomineralization process that is controlled by extracellular matrix proteins. The intrinsically disordered matrix protein ameloblastin (AMBN) is the most abundant nonamelogenin protein of the developing enamel and a key element for correct enamel formation. AMBN was suggested to be a cell adhesion molecule that regulates proliferation and differentiation of ameloblasts. Nevertheless, detailed structural and functional studies on AMBN have been substantially limited by the paucity of the purified nondegraded protein. With this study, we have developed a procedure for production of a highly purified form of recombinant human AMBN in quantities that allowed its structural characterization. Using size exclusion chromatography, analytical ultracentrifugation, transmission electron, and atomic force microscopy techniques, we show that AMBN self-associates into ribbon-like supramolecular structures with average widths and thicknesses of 18 and 0.34 nm, respectively. The AMBN ribbons exhibited lengths ranging from tens to hundreds of nm. Deletion analysis and NMR spectroscopy revealed that an N-terminal segment encoded by exon 5 comprises two short independently structured regions and plays a key role in self-assembly of AMBN. 相似文献
140.
Dariush Ilghari Lorna C. Waters Vaclav Veverka Frederick W. Muskett Mark D. Carr 《Biomolecular NMR assignments》2009,3(2):171-174
Comprehensive sequence specific 1H, 15N, and 13C resonance assignments are reported for the Mycobacterium tuberculosis Rv0287–Rv0288 protein complex. Analysis of the chemical shift data obtained indicates that each protein in the complex contains
two relatively long helical regions joined by an irregular loop. 相似文献