全文获取类型
收费全文 | 188篇 |
免费 | 14篇 |
出版年
2021年 | 8篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2017年 | 6篇 |
2016年 | 7篇 |
2015年 | 12篇 |
2014年 | 6篇 |
2013年 | 7篇 |
2012年 | 11篇 |
2011年 | 14篇 |
2010年 | 8篇 |
2009年 | 6篇 |
2008年 | 8篇 |
2007年 | 7篇 |
2006年 | 4篇 |
2005年 | 5篇 |
2004年 | 3篇 |
2003年 | 8篇 |
2002年 | 5篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1982年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有202条查询结果,搜索用时 15 毫秒
31.
Atkin JD Farg MA Turner BJ Tomas D Lysaght JA Nunan J Rembach A Nagley P Beart PM Cheema SS Horne MK 《The Journal of biological chemistry》2006,281(40):30152-30165
Mutations in Cu/Zn superoxide dismutase (SOD1) are linked to motor neuron death in familial amyotrophic lateral sclerosis (ALS) by an unclear mechanism, although misfolded SOD1 aggregates are commonly associated with disease. Proteomic analysis of the transgenic SOD1(G93A) ALS rat model revealed significant up-regulation of endoplasmic reticulum (ER)-resident protein-disulfide isomerase (PDI) family members in lumbar spinal cords. Expression of SOD1 mutants (mSOD1) led to an up-regulation of PDI in motor neuron-like NSC-34 cells but not other cell lines. Inhibition of PDI using bacitracin increased aggregate production, even in wild type SOD1 transfectants that do not readily form inclusions, suggesting PDI may protect SOD1 from aggregation. Moreover, PDI co-localized with intracellular aggregates of mSOD1 and bound to both wild type and mSOD1. SOD1 was also found in the microsomal fraction of cells despite being a predominantly cytosolic enzyme, confirming ER-Golgi-dependent secretion. In SOD1(G93A) mice, a significant up-regulation of unfolded protein response entities was also observed during disease, including caspase-12, -9, and -3 cleavage. Our findings therefore implicate unfolded protein response and ER stress-induced apoptosis in the patho-physiology of familial ALS. The possibility that PDI may be a therapeutic target to prevent SOD1 aggregation is also raised by this study. 相似文献
32.
The exact positioning of the membrane in transmembrane (TM) proteins plays important functional roles. Yet, the structures of TM proteins in protein data bank (pdb) have no information about the explicit position of the membrane. Using a simple hydrophobic lipid-protein mismatch energy function and a flexible lipid/water boundary, the position of lipid bilayer for representative TM proteins in pdb have been annotated. A web server called MAPS (Membrane Annotation of Protein Structures; available at: http://www.boseinst.ernet.in/gautam/maps) has been set up that allows the user to interactively analyze membrane-protein orientations of any uploaded pdb structure with user-defined membrane flexibility parameters. 相似文献
33.
Manjistha Sengupta Amrita Cheema Henry J. Kaminski Linda L. Kusner The Muscle Study Group 《PloS one》2014,9(7)
Prednisone is often used for the treatment of autoimmune and inflammatory diseases but they suffer from variable therapeutic responses and significant adverse effects. Serum biological markers that are modulated by chronic corticosteroid use have not been identified. Myasthenia gravis is an autoimmune neuromuscular disorder caused by antibodies directed against proteins present at the post-synaptic surface of neuromuscular junction resulting in weakness. The patients with myasthenia gravis are primarily treated with prednisone. We analyzed the metabolomic profile of serum collected from patients prior to and after 12 weeks of prednisone treatment during a clinical trial. Our aim was to identify metabolites that may be treatment responsive and be evaluated in future studies as potential biomarkers of efficacy or adverse effects. Ultra-performance liquid chromatography coupled with electro-spray quadrupole time of flight mass spectrometry was used to obtain comparative metabolomic and lipidomic profile. Untargeted metabolic profiling of serum showed a clear distinction between pre- and post- treatment groups. Chronic prednisone treatment caused upregulation of membrane associated glycerophospholipids: phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, 1, 2-diacyl-sn glycerol 3 phosphate and 1-Acyl-sn-glycero-3-phosphocholine. Arachidonic acid (AA) and AA derived pro-inflammatory eicosanoids such as 18-carboxy dinor leukotriene B4 and 15 hydroxyeicosatetraenoic acids were reduced. Perturbations in amino acid, carbohydrate, vitamin and lipid metabolism were observed. Chronic prednisone treatment caused increase in membrane associated glycerophospholipids, which may be associated with certain adverse effects. Decrease of AA and AA derived pro-inflammatory eicosanoids demonstrate that immunosuppression by corticosteroid is via suppression of pro-inflammatory pathways. The study identified metabolomic fingerprints that can now be validated as prednisone responsive biomarkers for the improvement in diagnostic accuracy and prediction of therapeutic outcome. 相似文献
34.
Muhammad Umar Cheema Helle Hasager Damkier Jakob Nielsen Ebbe Toftgaard Poulsen Jan J. Enghild Robert A. Fenton Jeppe Praetorius 《PloS one》2014,9(7)
Prolonged elevations of plasma aldosterone levels are associated with renal pathogenesis. We hypothesized that renal distress could be imposed by an augmented aldosterone-induced protein turnover challenging cellular protein degradation systems of the renal tubular cells. Cellular accumulation of specific protein aggregates in rat kidneys was assessed after 7 days of aldosterone administration. Aldosterone induced intracellular accumulation of 60 s ribosomal protein L22 in protein aggregates, specifically in the distal convoluted tubules. The mineralocorticoid receptor inhibitor spironolactone abolished aldosterone-induced accumulation of these aggregates. The aldosterone-induced protein aggregates also contained proteasome 20 s subunits. The partial de-ubiquitinase ataxin-3 was not localized to the distal renal tubule protein aggregates, and the aggregates only modestly colocalized with aggresome transfer proteins dynactin p62 and histone deacetylase 6. Intracellular protein aggregation in distal renal tubules did not lead to development of classical juxta-nuclear aggresomes or to autophagosome formation. Finally, aldosterone treatment induced foci in renal cortex of epithelial vimentin expression and a loss of E-cadherin expression, as signs of cellular stress. The cellular changes occurred within high, but physiological aldosterone concentrations. We conclude that aldosterone induces protein accumulation in distal renal tubules; these aggregates are not cleared by autophagy that may lead to early renal tubular damage. 相似文献
35.
36.
Histone variants play a critical role in chromatin structure and epigenetic regulation. These “deviant” proteins have been historically considered as the evolutionary descendants of ancestral canonical histones, helping specialize the nucleosome structure during eukaryotic evolution. Such view is now challenged by 2 major observations: first, canonical histones present extremely unique features not shared with any other genes; second, histone variants are widespread across many eukaryotic groups. The present work further supports the ancestral nature of histone variants by providing the first in vivo characterization of a functional macroH2A histone (a variant long defined as a specific refinement of vertebrate chromatin) in a non-vertebrate organism (the mussel Mytilus) revealing its recruitment into heterochromatic fractions of actively proliferating tissues. Combined with in silico analyses of genomic data, these results provide evidence for the widespread presence of macroH2A in metazoan animals, as well as in the holozoan Capsaspora, supporting an evolutionary origin for this histone variant lineage before the radiation of Filozoans (including Filasterea, Choanoflagellata and Metazoa). Overall, the results presented in this work help configure a new evolutionary scenario in which histone variants, rather than modern “deviants” of canonical histones, would constitute ancient components of eukaryotic chromatin. 相似文献
37.
Acacia senegal (L) Willd. is a small sized tree species of Tropical arid region of Southern West Pakistan. It is well-known for producing
gum arabic.
Fruits from dry streams with loamy sand soil type were of bigger size whereas seed output per pod and seed weight were higher
in hilly regions.
The seeds possess external dormancy (seed coat), which can be broken by mechanical and chemical scarification, water (cold
and boiling) and dark treatments. Seeds gave high percentage of germination in fine sand in pot culture. Germination percentage
was high in May–July. The growth rate of seedlings both in pot culture and field conditions was high in April, May, June and
July. Seeds collected from different localities showed considerable variation in germination capacity. Percentage and rate
of germination increased with the lapse of time.
Correlation of growth and abundance ofAcacia senegal was found with topography, soil texture, soil structure, soil consistence, maximum water holding capacity, wilting coefficient
(sub-surface soil), soil carbonates (surface soil) soil pH (surface soil) and community associates.
The plant can be propagated by shoot cuttings. Smaller and thinner cuttings are easily propagated.
The plant is infested by Buffaloe tree hopper and is also infected byCladosporium herbarum. Occasionally seedlings are attacked byFusarium sp.
The relative turgidity of branches was found to be high throughout the study period, but the leaves showed considerable variation. 相似文献
38.
During induction of somatic embryogenesis from immature embryos of soybean, a smooth-shiny and a rough callus were obtained. The smooth-shiny type developed from callus derived from cotyledonary tissue and cultured on media containing 10 mg/l 2,4-D. The rough type was derived from immature embryos, cotyledons, hypocotyls and hypocotyl segments from germinated seedlings on a medium containing various growth regulators. Plants were obtained from the smooth-shiny type but rough callus did not differentiate into plants. The conditions for formation of both callus types and regeneration of mature soybean plants from the smooth-shiny type were defined.Abbreviations 2,4-D
2,4-dichlorophenoxyacetic acid
- IAA
indoleacetic acid
- IBA
indolebutyric acid
- ABA
abscicic acid
- GA3
gibberellic acid
- BA
benzyladenine
- B5
Gamborg et al.
- LS
Linsmaier & Skoog
- MS
Murashige & Skoog
- P
proline 相似文献
39.
Choudhary SK Archin NM Cheema M Dahl NP Garcia JV Margolis DM 《Journal of virology》2012,86(1):114-120
Persistent human immunodeficiency virus type 1 (HIV-1) infection of resting CD4+ T cells, unaffected by antiretroviral therapy (ART), provides a long-lived reservoir of HIV infection. Therapies that target this viral reservoir are needed to eradicate HIV-1 infection. A small-animal model that recapitulates HIV-1 latency in resting CD4+ T cells may accelerate drug discovery and allow the rational design of nonhuman primate (NHP) or human studies. We report that in humanized Rag2−/− γc−/− (hu-Rag2−/− γc−/−) mice, as in humans, resting CD4+ T cell infection (RCI) can be quantitated in pooled samples of circulating cells and tissue reservoirs (e.g., lymph node, spleen, bone marrow) following HIV-1 infection with the CCR5-tropic JR-CSF strain and suppression of viremia by ART. Replication-competent virus was recovered from pooled resting CD4+ T cells in 7 of 16 mice, with a median frequency of 8 (range, 2 to 12) infected cells per million T cells, demonstrating that HIV-1 infection can persist despite ART in the resting CD4+ T cell reservoir of hu-Rag2−/− γc−/− mice. This model will allow rapid preliminary assessments of novel eradication approaches and combinatorial strategies that may be challenging to perform in the NHP model or in humans, as well as a rigorous analysis of the effect of these interventions in specific anatomical compartments. 相似文献
40.
Zeng W Seward HE Málnási-Csizmadia A Wakelin S Woolley RJ Cheema GS Basran J Patel TR Rowe AJ Bagshaw CR 《Biochemistry》2006,45(35):10482-10491
Green fluorescent protein and its variants are frequently used as F?rster (fluorescence) resonance energy transfer (FRET) pairs to determine the proximity of protein domains. We prepared fusion proteins comprising yellow fluorescent protein-Dictyostelium myosin II motor domain-cyan fluorescent protein (YFP-myosin-CFP) and compared their FRET properties with an existing construct (GFP-myosin-BFP), containing a green fluorescent protein acceptor and blue fluorescent protein donor [Suzuki, Y., Yasunaga, T., Ohkura, R., Wakabayashi, T. and Sutoh, K. (1998) Nature 396, 380-383]. The latter construct showed an apparent 40% reduction in acceptor fluorescence on ATP addition, when excited via the donor, compared with the YFP-myosin-CFP constructs which showed a small increase (相似文献