全文获取类型
收费全文 | 286篇 |
免费 | 22篇 |
出版年
2023年 | 3篇 |
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 5篇 |
2019年 | 10篇 |
2018年 | 9篇 |
2017年 | 8篇 |
2016年 | 10篇 |
2015年 | 7篇 |
2014年 | 11篇 |
2013年 | 17篇 |
2012年 | 22篇 |
2011年 | 23篇 |
2010年 | 17篇 |
2009年 | 13篇 |
2008年 | 16篇 |
2007年 | 24篇 |
2006年 | 13篇 |
2005年 | 15篇 |
2004年 | 16篇 |
2003年 | 17篇 |
2002年 | 13篇 |
2001年 | 3篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有308条查询结果,搜索用时 15 毫秒
21.
Alzheimer's disease is associated with the formation of paired helical filaments composed of hyperphospharylated tau protein. Phosphatase 2B, calcineurin can dephosphorylate the tau protein and, therefore, might prevent the assembly of paired helical filaments and even Alzheimer's disease. Calcipressin 1, the DSCR1(Adapt78) gene product, can bind and inactivate calcineurin. Here we hypothesize that while short-term induction of calcipressin1 can provide stress protection, its long-term or chronic induction may cause gradual accumulation of hyperphosphorylated tau protein, eventually leading to Alzheimer's disease. 相似文献
22.
Gennady Poda Bernard Maigret 《International journal of peptide research and therapeutics》1998,5(2-3):193-197
Summary Human σ opioid receptor (σOR), a G-protein-coupled receptor, has been modeled using the helix axes as revealed by the crystallographic
structure of bacteriorhodopsin and ligand binding profiles of single-point mutants of σOR. The model revealed feasibility
of existence of a second disulfide bridge between the transmembrane helices (TMHs) 6 and 7, Cys273-Cys303. A common binding site has been suggested for high-affinity selective agonists DPDPE, DPLPE, DTLET, BW373U86 and antagonist
Naltrindole. Docking calculations have shown that the amino group of the ligands forms a hydrogen bond with the imidazole
ring of His301 (TMH7) rather than with Asp128 (TMH3) and is not a cation counterpart of this highly conserved aspartyl residue. All the findings and the model shed light
on the putative structure and functioning of opioid receptors and can be used for designing further mutagenesis experiments. 相似文献
23.
Heli Elovaara Teija Huusko Mikael Maksimow Kati Elima Gennady G. Yegutkin Mikael Skurnik Ulrich Dobrindt Anja Siitonen Michael J. McPherson Marko Salmi Sirpa Jalkanen 《PloS one》2015,10(11)
Escherichia coli amine oxidase (ECAO), encoded by the tynA gene, catalyzes the oxidative deamination of aromatic amines into aldehydes through a well-established mechanism, but its exact biological role is unknown. We investigated the role of ECAO by screening environmental and human isolates for tynA and characterizing a tynA-deletion strain using microarray analysis and biochemical studies. The presence of tynA did not correlate with pathogenicity. In tynA+ Escherichia coli strains, ECAO enabled bacterial growth in phenylethylamine, and the resultant H2O2 was released into the growth medium. Some aminoglycoside antibiotics inhibited the enzymatic activity of ECAO, which could affect the growth of tynA+ bacteria. Our results suggest that tynA is a reserve gene used under stringent environmental conditions in which ECAO may, due to its production of H2O2, provide a growth advantage over other bacteria that are unable to manage high levels of this oxidant. In addition, ECAO, which resembles the human homolog hAOC3, is able to process an unknown substrate on human leukocytes. 相似文献
24.
ClC chloride channels and transporters play major roles in cellular excitability, epithelial salt transport, volume, pH, and blood pressure regulation. One family member, ClC-ec1 from Escherichia coli, has been structurally resolved crystallographically and subjected to intensive mutagenetic, crystallographic, and electrophysiological studies. It functions as a Cl−/H+ antiporter, not a Cl− channel; however, the molecular mechanism for Cl−/H+ exchange is largely unknown. Using all-atom normal-mode analysis to explore possible mechanisms for this antiport, we propose that Cl−/H+ exchange involves a conformational cycle of alternating exposure of Cl− and H+ binding sites of both ClC pores to the two sides of the membrane. Both pores switch simultaneously from facing outward to facing inward, reminiscent of the standard alternating-access mechanism, which may have direct implications for eukaryotic Cl−/H+ transporters and Cl− channels. 相似文献
25.
Luzyanina T Mrusek S Edwards JT Roose D Ehl S Bocharov G 《Journal of mathematical biology》2007,54(1):57-89
CFSE based tracking of the lymphocyte proliferation using flow cytometry is a powerful experimental technique in immunology
allowing for the tracing of labelled cell populations over time in terms of the number of divisions cells undergone. Interpretation
and understanding of such population data can be greatly improved through the use of mathematical modelling. We apply a heterogenous
linear compartmental model, described by a system of ordinary differential equations similar to those proposed by Kendall.
This model allows division number-dependent rates of cell proliferation and death and describes the rate of changes in the
numbers of cells having undergone j divisions. The experimental data set that we specifically analyze specifies the following characteristics of the kinetics
of PHA-induced human T lymphocyte proliferation assay in vitroL (1) the total number of live cells, (2) the total number of
dead but not disintegrated cells and (3) the number of cells divided j times. Following the maximum likelihood approach for data fitting, we estimate the model parameters which, in particular,
present the CTL birth- and death rate “functions”. It is the first study of CFSE labelling data which convincingly shows that
the lymphocyte proliferation and death both in vitro and in vivo are division number dependent. For the first time, the confidence
in the estimated parameter values is analyzed by comparing three major methods: the technique based on the variance–covariance
matrix, the profile-likelihood-based approach and the bootstrap technique. We compare results and performance of these methods
with respect to their robustness and computational cost. We show that for evaluating mathematical models of differing complexity
the information-theoretic approach, based upon indicators measuring the information loss for a particular model (Kullback–Leibler
information), provides a consistent basis. We specifically discuss methodological and computational difficulties in parameter
identification with CFSE data, e.g. the loss of confidence in the parameter estimates starting around the sixth division.
Overall, our study suggests that the heterogeneity inherent in cell kinetics should be explicitly incorporated into the structure
of mathematical models.
相似文献
26.
Guliy OI Matora LY Burygin GL Dykman LA Ostudin NA Bunin VD Ignatov VV Ignatov OV 《Analytical biochemistry》2007,370(2):201-205
This work was undertaken to examine the electrooptical characteristics of cells of Azospirillum brasilense Sp245 during their interaction with antibodies developed to various cell surface epitopes. We used the dependences of the cell suspension optical density changes induced by electroorientation on the orienting field frequency (740, 1000, 1450, 2000, and 2800kHz). Cell interactions with homologous strain-specific antibodies to the A. brasilense Sp245 O antigen and with homologous antibodies to whole bacterial cells brought about considerable changes in the electrooptical properties of the bacterial suspension. When genus-specific antibodies to the flagellin of the Azospirillum sheathed flagellum and antibodies to the serologically distinct O antigen of A. brasilense Sp7 were included in the A. brasilense Sp245 suspension, the changes caused in the electrooptical signal were slight and had values close to those for the above changes. These findings agree well with the immunochemical characteristics of the Azospirillum O antigens and with the data on the topographical distribution of the Azospirillum major cell surface antigens. The obtained results can serve as a basis for the development of a rapid test for the intraspecies detection of microorganisms. 相似文献
27.
Adrenergic receptor density in brown adipose tissue of active and hibernating hamsters and ground squirrels 总被引:1,自引:0,他引:1
Kramarova LI Bronnikov GE Ignat'ev DA Cannon B Nedergaard J 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,146(3):408-414
The ligand-binding characteristics (B(max) and K(D)) of alpha(1)- and beta(1)/beta(2)-adrenoceptors were investigated in membranes prepared from brown adipose tissue (BAT) of warm-acclimated, cold-acclimated, hibernating and arousing ground squirrels (Spermophillus undulatus) and hamsters (Mesocricetus auratus) by specific binding of [(3)H]prazosin and [(3)H]CGP-12177, respectively. The physiological state did not change the affinity for the adrenoceptors in the BAT of ground squirrels and hamsters. There was a significant decrease in alpha(1)-receptor density in arousing ground squirrels and a significant decrease in beta(1)/beta(2) density in hibernating ground squirrels. The level of alpha(1)-receptors was in all conditions higher than that of beta(1)/beta(2) receptors. The results indicate a possible change in balance of adrenoceptor density in the processes of cold acclimation, hibernation and arousal. The balance between the various adrenoceptor subtypes may be important for the final effect of catecholamines in BAT in different physiological states. 相似文献
28.
Lada V. Stepanova Gennady L. Burygin Valentina E. Nikitina Olga M. Tsivileva 《World journal of microbiology & biotechnology》2011,27(7):1579-1585
Both quantitative and qualitative estimations of the basidiomycete Grifola frondosa lectin binding to the specific and non-specific polyclonal rabbit antibodies were attempted. The lectin complexation with
homological antibodies was shown to be characterized by greater binding constants as compared to non-homological antibodies.
Therewith the values of changes in standard free energy ∆G
0 displaying a strength of both complexes were essentially the same. The data obtained testify to universality of biospecific
reactions “antigen–antibody” and “lectin–carbohydrate” at a molecular level, and could give new insight into the phenomenon
of these biospecific interactions. The actual specificity in the above bio-recognition processes could differ from the results
of in vitro assays using lectins, and, therefore, should be interpreted carefully when concluding on the lectins behaviour
in living systems. 相似文献
29.
Matts RL Brandt GE Lu Y Dixit A Mollapour M Wang S Donnelly AC Neckers L Verkhivker G Blagg BS 《Bioorganic & medicinal chemistry》2011,19(1):684-692
Several Hsp90 modulators have been identified including the N-terminal ligand geldanamycin (GDA), the C-terminal ligand novobiocin (NB), and the co-chaperone disruptor celastrol. Other Hsp90 modulators elicit a mechanism of action that remains unknown. For example, the natural product gedunin and the synthetic anti-spermatogenic agent H2-gamendazole, recently identified Hsp90 modulators, manifest biological activity through undefined mechanisms. Herein, we report a series of biochemical techniques used to classify such modulators into identifiable categories. Such studies provided evidence that gedunin and H2-gamendazole both modulate Hsp90 via a mechanism similar to celastrol, and unlike NB or GDA. 相似文献
30.