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931.
Alina Kułakowska Nicholas J Ciccarelli Qi Wen Barbara Mroczko Wiesław Drozdowski Maciej Szmitkowski Paul A Janmey Robert Bucki 《BMC neurology》2010,10(1):107
Background
Extracellular gelsolin (GSN) and GC-globulin/Vitamin D-binding protein (DBP) appear to play an important role in clearing the actin from extracellular fluids and in modulating cellular responses to anionic bioactive lipids. In this study we hypothesized that cellular actin release and/or increase in bioactive lipids associated with multiple sclerosis (MS) development will translate into alteration of the actin scavenger system protein concentrations in blood and cerebrospinal fluid (CSF) of patients with MS. 相似文献932.
Augustin C. Mot Alina Roman Iulia Lupan Donald M. KurtzJr Radu Silaghi-Dumitrescu 《The protein journal》2010,29(6):387-393
Hemerythrin is proposed as an alternative to hemoglobin-based blood substitutes. In contrast to hemoglobin, hemerythrin exhibits
negligible reactivity towards oxidative and nitrosative stress agents (peroxide, nitric oxide, nitrite). Protocols for attachment
of polyethylene glycol and glutaraldehyde cross-linking of Hr are described. These derivatizations appear to have favorable
effects on O2 affinity and autoxidation rates for use in blood substitutes. Based on lessons learned from hemoglobin-based blood substitutes,
these derivatizations should also help limit extravasation and antigenicity of a hemerythrin-based blood substitute. 相似文献
933.
Piazza P McMurtrey CP Lelic A Cook RL Hess R Yablonsky E Borowski L Loeb MB Bramson JL Hildebrand WH Rinaldo CR 《PloS one》2010,5(12):e15343
West Nile virus (WNV) infection can result in severe neuroinvasive disease, particularly in persons with advanced age. As rodent models demonstrate that T cells play an important role in limiting WNV infection, and strong T cell responses to WNV have been observed in humans, we postulated that inadequate antiviral T cell immunity was involved in neurologic sequelae and the more severe outcomes associated with age. We previously reported the discovery of six HLA-A*0201 restricted WNV peptide epitopes, with the dominant T cell targets in naturally infected individuals being SVG9 (Env) and SLF9 (NS4b). Here, memory phenotype and polyfunctional CD8+ T cell responses to these dominant epitopes were assessed in 40 WNV seropositive patients displaying diverse clinical symptoms. The patients' PBMC were stained with HLA-I multimers loaded with the SVG9 and SLF9 epitopes and analyzed by multicolor flow cytometry. WNV-specific CD8+ T cells were found in peripheral blood several months post infection. The number of WNV-specific T cells in older individuals was the same, if not greater, than in younger members of the cohort. WNV-specific T cells were predominantly monofunctional for CD107a, MIP-1β, TNFα, IL-2, or IFNγ. When CD8+ T cell responses were stratified by disease severity, an increased number of terminally differentiated, memory phenotype (CD45RA+ CD27- CCR7- CD57+) T cells were detected in patients suffering from viral neuroinvasion. In conclusion, T cells of a terminally differentiated/cytolytic profile are associated with neuroinvasion and, regardless of age, monofunctional T cells persist following infection. These data provide the first indication that particular CD8+ T cell phenotypes are associated with disease outcome following WNV infection. 相似文献
934.
Beverly Duncan Cristina Nazarov–Stoica Jacqueline Surls Margaret Kehl Constantin Bona Sofia Casares Teodor-D. Brumeanu 《PloS one》2010,5(7)
Background
Double negative CD3+4−8− TCRαβ splenic cells (DNCD3) can suppress the immune responses to allo and xenografts, infectious agents, tumors, and some autoimmune disorders. However, little is known about their role in autoimmune diabetes, a disease characterized by the reduction of insulin production subsequent to destruction of pancreatic β-cells by a polyclonal population of self-reactive T-cells. Herein, we analyzed the function and phenotype of DNCD3 splenic cells in young NOD mice predisposed to several autoimmune disorders among which, the human-like autoimmune diabetes.Methodology/Principal Findings
DNCD3 splenic cells from young NOD mice (1) provided long-lasting protection against diabetes transfer in NOD/Scid immunodeficient mice, (2) proliferated and differentiated in the spleen and pancreas of NOD/Scid mice and pre-diabetic NOD mice into IL-10-secreting TR-1 like cells in a Th2-like environment, and (3) their anti-diabetogenic phenotype is CD3+(CD4−CD8−)CD28+CD69+CD25low Foxp3− iCTLA-4−TCRαβ+ with a predominant Vβ13 gene usage.Conclusions/Significance
These findings delineate a new T regulatory component in autoimmune diabetes apart from that of NKT and CD4+CD25high Foxp3+T-regulatory cells. DNCD3 splenic cells could be potentially manipulated towards the development of autologous cell therapies in autoimmune diabetes. 相似文献935.
936.
Rebecca Anderson Angels Franch Margarida Castell Francisco J Perez-Cano Rolf Bräuer Dirk Pohlers Mieczyslaw Gajda Alexandros P Siskos Theodora Katsila Constantin Tamvakopoulos Una Rauchhaus Steffen Panzner Raimund W Kinne 《Arthritis research & therapy》2010,12(4):1-15
Introduction
The objective of this study was to evaluate the efficacy of intravenous (i.v.) injection of liposomally encapsulated dexamethasone phosphate (DxM-P) in comparison to free DxM-P in rats with established adjuvant arthritis (AA). This study focused on polyethylene glycol (PEG)-free liposomes, to minimize known allergic reactions caused by neutral PEG-modified (PEG-ylated) liposomes.Methods
Efficacy was assessed clinically and histologically using standard scores. Non-specific and specific immune parameters were monitored. Activation of peritoneal macrophages was analyzed via cytokine profiling. Pharmacokinetics/biodistribution of DxM in plasma, synovial membrane, spleen and liver were assessed via mass spectrometry.Results
Liposomal DxM-P (3 × 1 mg/kg body weight; administered intravenously (i.v.) on Days 14, 15 and 16 of AA) suppressed established AA, including histological signs, erythrocyte sedimentation rate, white blood cell count, circulating anti-mycobacterial IgG, and production of interleukin-1beta (IL-1β) and IL-6 by peritoneal macrophages. The suppression was strong and long-lasting. The clinical effects of liposomal DxM-P were dose-dependent for dosages between 0.01 and 1.0 mg/kg. Single administration of 1 mg/kg liposomal DxM-P and 3 × 1 mg/kg of free DxM-P showed comparable effects consisting of a partial and transient suppression. Moreover, the effects of medium-dose liposomal DxM-P (3 × 0.1 mg/kg) were equal (in the short term) or superior (in the long term) to those of high-dose free DxM-P (3 × 1 mg/kg), suggesting a potential dose reduction by a factor between 3 and 10 by liposomal encapsulation. For at least 48 hours after the last injection, the liposomal drug achieved significantly higher levels in plasma, synovial membrane, spleen and liver than the free drug.Conclusions
This new PEG-free formulation of macrophage-targeting liposomal DxM-P considerably reduces the dose and/or frequency required to treat AA, with a potential to enhance or prolong therapeutic efficacy and limit side-effects also in the therapy of rheumatoid arthritis. Depot and/or recirculation effects in plasma, inflamed joint, liver, and spleen may contribute to this superiority of liposomally encapsulated DxM-P. 相似文献937.
Cristina Stan Constantin P. Cristescu Eugen I. Scarlat 《Journal of theoretical biology》2010,267(4):513-518
Using chaos game representation we introduce a novel and straightforward method for identifying similarities/dissimilarities between DNA sequences of the same type, from different organisms. A matrix is associated to each CGR pattern and the similarities result from the comparison between the matrices of the sequences of interest. Three different methods of analysis of the resulting difference matrix are considered: a 3-dimensional representation giving both local and global information, a numerical characterization by defining an n-letter word similarity measure and a statistical evaluation. The method is illustrated by implementation to the study of albumin nucleotides sequences from eight mammal species taking as reference the human albumin. 相似文献
938.
Nechifor MT Constantin C Manda G Neagu M Dinu D 《Roumanian archives of microbiology and immunology》2006,65(3-4):135-140
We report the effects of reactive oxygen species generated by ultraviolet-A radiation on some biochemical parameters specific for oxidative stress, in rat testis homogenates. Results show an increase in lipid peroxidation products under ultraviolet-A exposure, and suggest that the involved mechanism is typical for a radical-mediated chain reaction. The amount of SH groups also increases during irradiation, probably as a consequence of conformational changes in proteins. Electrophoresis results revealed protein pattern changes mainly in the low molecular weight domain. The catalytic activities of alkaline phosphatase and gamma-glutamil transpeptidase are modified under the oxidative conditions generated by reactive oxygen species. The changes of the enzymatic activities are UVA exposure time-dependent, suggesting that conformational modifications are responsible for enzymatic activities enhancement. 相似文献
939.
Arabski M Kazmierczak P Wiśniewska-Jarosińska M Morawiec Z Morawiec-Bajda A Klupińska G Drzewoski J Chojnacki J Błasiak J 《Cellular & molecular biology letters》2006,11(4):570-578
The pathogenesis of stomach cells can be associated with their susceptibility to exogenous dietary irritants, like nitrosamines
such as dimethylnitrosamines (DMNA), and to the effects of non-dietary factors, including Helicobacter pylori infection. We used N-methyl-N’-nitro N-nitrosoguanidyne (MNNG) as a surrogate agent that induces a spectrum of DNA damage similar to DMNA. Using the alkaline comet
assay, we showed that antioxidants — vitamins C and E, quercetin, and melatonin — reduced the genotoxic effect of MNNG in
H. pylori-infected and non-infected human gastric mucosa cells (GMCs). To compare the sensitivity of the stomach and the blood, the
experiment was also carried out in peripheral blood. We observed a higher level of DNA damage induced by MNNG in H. pylori-infected than in noninfected GMCs. We did not note any difference in the efficacy of the repair of the damage in either type
of GMC. H. pylori infection may play an important role in the pathogenesis of GMCs, as it can modulate their susceptibility to dietary mutagens/carcinogens,
thus contributing to gastric cancer. 相似文献
940.
Ian A Clark Alison C Budd Gunther Hsue Bret R Haymore Alina J Joyce Richard Thorner Peter J Krause 《Malaria journal》2006,5(1):1-3