全文获取类型
收费全文 | 219篇 |
免费 | 10篇 |
出版年
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 7篇 |
2016年 | 7篇 |
2015年 | 6篇 |
2014年 | 8篇 |
2013年 | 17篇 |
2012年 | 20篇 |
2011年 | 15篇 |
2010年 | 9篇 |
2009年 | 8篇 |
2008年 | 8篇 |
2007年 | 21篇 |
2006年 | 9篇 |
2005年 | 8篇 |
2004年 | 12篇 |
2003年 | 10篇 |
2002年 | 11篇 |
2000年 | 2篇 |
1999年 | 9篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1986年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1976年 | 1篇 |
排序方式: 共有229条查询结果,搜索用时 18 毫秒
1.
2.
Harish Kumar Jayant B. Udgaonkar 《Protein science : a publication of the Protein Society》2021,30(4):785
Amyloid fibrillar aggregates isolated from the brains of patients with neurodegenerative diseases invariably have post‐translational modifications (PTMs). The roles that PTMs play in modulating the structures and polymorphism of amyloid aggregates, and hence their ability to catalyze the conversion of monomeric protein to their fibrillar structure is, however, poorly understood. This is particularly true in the case of tau aggregates, where specific folds of fibrillar tau have been implicated in specific tauopathies. Several PTMs, including acetylation at Lys 280, increase aggregation of tau in the brain, and increase neurodegeneration. In this study, tau‐K18 K280Q, in which the Lys 280 → Gln mutation is used to mimic acetylation at Lys 280, is shown, using HX‐MS measurements, to form fibrils with a structural core that is longer than that of tau‐K18 fibrils. Measurements of critical concentrations show that the binding affinity of monomeric tau‐K18 for its fibrillar counterpart is only marginally more than that of monomeric tau‐K18 K280Q for its fibrillar counterpart. Quantitative analysis of the kinetics of seeded aggregation, using a simple Michaelis–Menten‐like model, in which the monomer first binds and then undergoes conformational conversion to β‐strand, shows that the fibrils of tau‐K18 K280Q convert monomeric protein more slowly than do fibrils of tau‐K18. In contrast, monomeric tau‐K18 K280Q is converted faster to fibrils than is monomeric tau‐K18. Thus, the effect of Lys 280 acetylation on tau aggregate propagation in brain cells is expected to depend on the amount of acetylated tau present, and on whether the propagating seed is acetylated at Lys 280 or not. 相似文献
3.
Benoît F. Morel Meghan A. Burke Jayant Kalagnanam Susan A. McCarthy David J. Tweardy Penelope A. Morel 《Bulletin of mathematical biology》1996,58(3):569-594
The cytokines are the information superhighway of the immune system. They are an important component of the integrated behavior
of the system. In order to be able to have a good understanding of the immune system, we must be able to model the effect
of cytokines and their combined effect. This work is a step in that direction. We study the combined effect of two cytokines:
interleukin-2 (IL-2) and interleukin-4 (IL-4) on some cells of the immune system.
Interleukin-2 and interleukin-4 are important growth and differentiation factors for B and T cells. Interleukin-4 antagonizes
the effect of interleukin-2 on B cells and some T cells while it synergizes with interleukin-2 on other T cells. We build
a mathematical model of the interaction of both cytokines on T and B cells as a building block toward a model of the Th1/Th2
cross-regulation. The response of a given cell to the combination of interleukin-2 and interleukin-4 is shown to involve competing
dynamical effects which can lead to either antagnostic or synergistic combined effect.
Author to whom correspondence should be addressed at Department of Engineering and Public Policy. Work supported by NIH grant
nv: Ai31427. 相似文献
4.
S M Kotwal M I Khan J M Khire 《Journal of industrial microbiology & biotechnology》1995,15(2):116-120
The thermophilic fungus,Humicola sp isolated from soil, secreted extracellular -galactosidase in a medium cotaining wheat bran extract and yeast extract. Maximum enzyme production was found in a medium containing 5% wheat bran extract as a carbon source and 0.5% beef extract as a carbon and nitrogen source. Enzyme secretion was strongly inhibited by the presence of Cu2+, Ni2+ and Hg2+ (1mM) in the fermentation medium. Production of enzyme under stationary conditions resulted in 10-fold higher activity than under shaking conditions. The temperature range for production of the enzyme was 37° C to 55°C, with maximum activity (5.54 U ml–1) at 45°C. Optimum pH and temperature for enzyme activity were 5.0 and 60° C respectively. One hundred per cent of the original activity was retained after heating the enzyme at 60°C for 1 h. At 5mM Hg2+ strongly inhibited enzyme activity. TheK
m andV
max forp-nitrophenyl--d-galactopyranoside were 60M and 33.6 mol min–1 mg–1, respectively, while for raffinose those values were 10.52 mM and 1.8 mol min–1 mg–1, respectively. 相似文献
5.
Butler Michael J. Aphale Jayant S. DiZonno Michele A. Krygsman Phyllis Walczyk Eva Malek Lawrence T. 《Journal of industrial microbiology & biotechnology》1994,13(1):24-29
Summary We have investigated the aminopeptidase activities present inStreptomyces lividans strains. The majority of these activities proved to be intracellular with multiple active species. Two aminopeptidase P genes were identified to be responsible for the ability to hydrolyze amino terminal peptide bonds adjacent to proline residues. Two other broad spectrum aminopeptidases were found to display homology at both the DNA and protein levels. One showed significant homology to PepN proteins, particularly around the putative zinc-binding residues which are important for catalysis. The second broad spectrum activity was not analyzed in detail but showed a different spectrum of substrate specificity to that of PepN. 相似文献
6.
H. G. Vartak M. C. Srinivasan V. K. Powar M. V. Rele J. M. Khire 《Biotechnology letters》1984,6(8):493-494
Summary Specific glucose and xylose isomerases have been identified in cell-free culture filtrates of a Chainia species. Treatment with DEAE-cellulose selectively adsorbed xylose isomerase activity while only the glucose isomerase was adsorbed on CM-cellulose. Glucose isomerase was completely inhibited by xylose at 1.3 × 10-4 M concentration. The differential identity of the extracellular glucose and xylose isomerases, unique to Chainia, is discussed.(NCL Communication 3562) 相似文献
7.
A new variant of hereditary hemolytic anemia in a family due to high adenosine triphosphate (ATP) is reported. The increase in ATP levels varied from 83 to 105% in the family members. Low 2,3-diphosphoglycerate levels and low 2,3-diphosphoglyceromutase activity were observed in three family members, with normal glucose-6-phosphate dehydrogenase and pyruvate kinase activity. 相似文献
8.
Nury M. Steuerwald David M. Foureau H. James Norton Jie Zhou Judith C. Parsons Naga Chalasani Robert J. Fontana Paul B. Watkins William M. Lee K. Rajender Reddy Andrew Stolz Jayant Talwalkar Timothy Davern Dhanonjoy Saha Lauren N. Bell Huiman Barnhart Jiezhun Gu Jose Serrano Herbert L. Bonkovsky 《PloS one》2013,8(12)
Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the United-States. The aim of the study was to describe serum immune profiles associated with acute DILI, to investigate whether there are profiles associated with clinical features or types of DILI and/or with prognosis, and to assess temporal changes in levels. Twenty-seven immune analytes were measured in the sera of 78 DILI subjects in the Drug-Induced Liver Injury Network (DILIN) and compared with 40 healthy controls. Immune analytes (14 cytokines, 7 chemokines and 6 growth factors) were measured by BioPlex multiplex ELISA at DILI onset and after 6 months. A modeling process utilizing immune principles was used to select a final set of variables among 27 immune analytes and several additional clinical lab values for prediction of early death (within 6 months of DILI onset). Nineteen of the 27 immune analytes were differentially expressed among healthy control, DILI onset and 6-month cohorts. Disparate patterns of immune responses, especially innate and adaptive cellular (mostly TH17) immunity were evident. Low values of four immune analytes (IL-9, IL-17, PDGF-bb and RANTES) and serum albumin are predictive of early death [PPV = 88% (95% CI, 65%-100%), NPV = 97% (95% CI, 93%-100%), accuracy = 96% (95% CI, 92%-100%)].
Conclusions
Acute DILI is associated with robust and varying immune responses. High levels of expression of cytokines associated with innate immunity are associated with a poor prognosis, whereas high levels of expression of adaptive cytokines are associated with good long-term prognosis and eventual recovery. Serum immune analyte profiles at DILI onset appear to be of prognostic, and perhaps, diagnostic significance. 相似文献9.
Jayant Pralhad Rathod Gunjan Prakash Reena Pandit Arvind M. Lali 《Photosynthesis research》2013,118(1-2):141-146
Parachlorella kessleri is a unicellular alga which grows in fresh as well as marine water and is commercially important as biomass/lipid feedstock and in bioremediation. The present study describes the successful transformation of marine P. kessleri with the help of Agrobacterium tumefaciens. Transformed marine P. kessleri was able to tolerate more than 10 mg l?1 hygromycin concentration. Co-cultivation conditions were modulated to allow the simultaneous growth of both marine P. kessleri and A. tumefaciens. For co-cultivation, P. kessleri was shifted from Walne’s to tris acetate phosphate medium to reduce the antibiotic requirement during selection. In the present study, the transfer of T-DNA was successful without using acetosyringone. Biochemical and genetic analyses were performed for expression of transgenes by GUS assay and PCR in transformants. Establishment of this protocol would be useful in further genetic modification of oil-bearing Parachlorella species. 相似文献
10.
The molecular integrity of the active site of phytases from fungi is critical for maintaining phytase function as efficient catalytic
machines. In this study, the molecular dynamics (MD) of two monomers of phytase B from Aspergillus niger, the disulfide intact
monomer (NAP) and a monomer with broken disulfide bonds (RAP), were simulated to explore the conformational basis of the
loss of catalytic activity when disulfide bonds are broken. The simulations indicated that the overall secondary and tertiary
structures of the two monomers were nearly identical but differed in some crucial secondary–structural elements in the vicinity of
the disulfide bonds and catalytic site. Disulfide bonds stabilize the β-sheet that contains residue Arg66 of the active site and
destabilize the α-helix that contains the catalytic residue Asp319. This stabilization and destabilization lead to changes in the shape
of the active–site pocket. Functionally important hydrogen bonds and atomic fluctuations in the catalytic pocket change during the
RAP simulation. None of the disulfide bonds are in or near the catalytic pocket but are most likely essential for maintaining the
native conformation of the catalytic site.