全文获取类型
收费全文 | 5323篇 |
免费 | 423篇 |
国内免费 | 1篇 |
专业分类
5747篇 |
出版年
2024年 | 5篇 |
2023年 | 31篇 |
2022年 | 71篇 |
2021年 | 144篇 |
2020年 | 77篇 |
2019年 | 96篇 |
2018年 | 143篇 |
2017年 | 107篇 |
2016年 | 190篇 |
2015年 | 269篇 |
2014年 | 280篇 |
2013年 | 400篇 |
2012年 | 436篇 |
2011年 | 487篇 |
2010年 | 297篇 |
2009年 | 256篇 |
2008年 | 305篇 |
2007年 | 354篇 |
2006年 | 294篇 |
2005年 | 262篇 |
2004年 | 266篇 |
2003年 | 244篇 |
2002年 | 198篇 |
2001年 | 45篇 |
2000年 | 37篇 |
1999年 | 43篇 |
1998年 | 53篇 |
1997年 | 40篇 |
1996年 | 41篇 |
1995年 | 31篇 |
1994年 | 25篇 |
1993年 | 18篇 |
1992年 | 22篇 |
1991年 | 19篇 |
1990年 | 21篇 |
1989年 | 14篇 |
1988年 | 12篇 |
1987年 | 6篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1981年 | 9篇 |
1980年 | 4篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1976年 | 5篇 |
1973年 | 5篇 |
1971年 | 6篇 |
1935年 | 4篇 |
排序方式: 共有5747条查询结果,搜索用时 15 毫秒
81.
José A Gómez-Puerta Raquel Celis M Victoria Hernández Virginia Ruiz-Esquide Julio Ramírez Isabel Haro Juan D Ca?ete Raimon Sanmartí 《Arthritis research & therapy》2013,15(6):R182
Introduction
Comparative data on synovial cell infiltrate and cytokine levels in anti citrullinated peptide/protein antibody (ACPA)-positive and ACPA negative rheumatoid arthritis (RA) patients are scarce. Our aim was to analyze synovial cell infiltrate and synovial fluid (SF) levels of cytokines in patients with RA according to the presence or absence of ACPA in serum.Methods
A cross-sectional study in a single center including consecutive RA patients was performed. Patients were defined as ''ACPA negative'' if serum was negative to two different ACPAs [second generation commercial anti-cyclic citrullinated peptide antibodies (CCP2) and chimeric fibrin/filaggrin citrullinated antibodies]. Parallel synovial tissue (ST) biopsies and SF were obtained by knee arthroscopy. Synovial cell infiltrate and endothelial cells were analyzed by immunohistochemistry and SF levels of Th1, Th2, Th17 and pro-inflammatory cytokines by Quantibody(R) Human Array.Results
A total of 83 patients underwent arthroscopy, with a mean age of 55.9 ± 12 years, and mean disease duration of 45 months (interquartile range, IQR 10.8 to 122). 62% were female and 77% were ACPA positive. No significant differences were found in clinical variables, acute phase reactants, synovial cell infiltrate or lymphoid neogenesis (LN) between ACPA positive and negative patients. However ACPA positive patients had significantly higher levels of IL-1β, IL-10, IL-17 F and CC chemokine ligand 20 (CCL-20) than ACPA negative patients.Conclusions
In our cohort of patients with RA no significant differences were found in synovial cell infiltrate or synovial LN according to ACPA status. However, ACPA positive patients had higher levels of T-cell derived and pro-inflammatory cytokines than ACPA negative patients. As systemic and local inflammation was similar in the two groups, these findings support a distinct synovial physiopathology. 相似文献82.
Ana Cristina Amado Laurentiu Bujor Isabel Monteiro Grillo 《Reports of Practical Oncology and Radiotherapy》2013,18(5):261-264
Aim
The purpose of this study was to evaluate acute and late toxicity and the locoregional control in patients treated with hypofractionated radical radiotherapy 2.25 Gy/fraction/day for early glottic carcinoma.Materials and methods
A retrospective analysis was performed of 27 patients, stage T1–T2 N0 glottic squamous cell carcinoma, that underwent radical RT from April 2008 to October 2011. The mean age was 64.6 years (range 36–81). Seventeen patients were staged T1a, 3 patients T1b and 7 patients T2. All patients were 3D planned and treated in a 6 MV LINAC, 2.25 Gy/fraction/5 days per week, to a total dose between 63 Gy and 67.5 Gy. Biological Effective Dose (BED (α/β = 10)) ranged from 77.18 Gy to 82.69 Gy and EQD2 from 64.31 Gy to 68.91 Gy. Patients were evaluated in periodic follow-up. Toxicity was evaluated according to RTOG Toxicities Scales.Results
With a median follow-time of 24.7 months (range 3.6–44.2 months), no evidence of locoregional recurrence was observed. The treatment was well tolerated and no unscheduled interruptions in treatments for toxicity were documented, with the median overall treatment time of 41 days (range 38–48). Only grades 1 and 2 acute toxicity were observed and no evidence of severe late toxicity.Conclusion
The authors believe that this moderately hypofractionated scheme can provide a good locoregional control for T1–T2 glottic carcinomas with no increase of toxicity. As the limitation of this work is the reduced number of patients and the lack of long term follow-up, the authors hope to update this retrospective study in the future in order to improve the power of the results. 相似文献83.
Karine Lambou Andrea Pennati Isabel Valsecchi Rui Tada Stephen Sherman Hajime Sato Remi Beau Giovanni Gadda Jean-Paul Latgé 《Eukaryotic cell》2013,12(6):853-863
The choline oxidase (CHOA) and betaine aldehyde dehydrogenase (BADH) genes identified in Aspergillus fumigatus are present as a cluster specific for fungal genomes. Biochemical and molecular analyses of this cluster showed that it has very specific biochemical and functional features that make it unique and different from its plant and bacterial homologs. A. fumigatus ChoAp catalyzed the oxidation of choline to glycine betaine with betaine aldehyde as an intermediate and reduced molecular oxygen to hydrogen peroxide using FAD as a cofactor. A. fumigatus Badhp oxidized betaine aldehyde to glycine betaine with reduction of NAD+ to NADH. Analysis of the AfchoAΔ::HPH and AfbadAΔ::HPH single mutants and the AfchoAΔAfbadAΔ::HPH double mutant showed that AfChoAp is essential for the use of choline as the sole nitrogen, carbon, or carbon and nitrogen source during the germination process. AfChoAp and AfBadAp were localized in the cytosol of germinating conidia and mycelia but were absent from resting conidia. Characterization of the mutant phenotypes showed that glycine betaine in A. fumigatus functions exclusively as a metabolic intermediate in the catabolism of choline and not as a stress protectant. This study in A. fumigatus is the first molecular, cellular, and biochemical characterization of the glycine betaine biosynthetic pathway in the fungal kingdom. 相似文献
84.
María José Buitrago Cristina Elena Canteros Guadalupe Frías De León Ángel González Manoel Marques-Evangelista De Oliveira César O. Muñoz José Antonio Ramirez Adriana Isabel Toranzo Rosely Zancope-Oliveira Manuel Cuenca-Estrella 《Revista iberoamericana de micología》2013,30(4):256-260
BackgroundA multicenter study was conducted. A panel containing DNA from Histoplasma capsulatum, as well as negative and cross-reaction controls, was sent to five different laboratories, members of the MICOMOL network from CYTED Program.AimsThe objective was to assess the accuracy of different PCR protocols to detect H. capsulatum DNA.MethodsSeven different PCR protocols were tested. They were based on PCR techniques and used unicopy and multicopy targets.ResultsMost of these protocols (4/7) were able to detect the smallest amounts of fungal DNA (102 fg/μl). Overall sensitivity was 86% and specificity was 100%. The protocol based on a unicopy target (SCAR220) presented lower sensitivity (43%) but 100% specificity. The real-time protocols tested were highly reproducible, sensitive, and specific. Neither false positives nor cross-reactions were detected in any protocol.ConclusionsAll laboratories were able to amplify H. capsulatum DNA, and real-time PCR seems to be a promising tool to efficiently detect this pathogen in clinical samples. 相似文献
85.
Mário S. Diniz Hugo M. Santos Pedro M. Costa Isabel Peres Maria H. Costa José L. Capelo 《Biomarkers》2013,18(6):589-598
The main objective of this work was to evaluate arsenic effects on metallothionein (MT) induction by exposing a freshwater Asiatic clam (Corbicula fluminea) to different concentrations of this metalloid. The presence of MT-like proteins was detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis and compared with a standard rabbit MT. In addition, the polarographic response showed good correspondence between standard MT and MT-like curves from C. fluminea, allowing MT quantification. The results show that clams exposed to different concentrations of arsenic are able to induce significant levels of MTs. Although variability was found in MT induction, significant differences in MT levels were found after 28 days of exposure in all treatments in comparison with the controls, suggesting that exposure to arsenic induced MT-like proteins in C. fluminea. 相似文献
86.
87.
Sara Violante Lodewijk IJlst Heleen te Brinke Janet Koster Isabel Tavares de Almeida Ronald J.A. Wanders Fátima V. Ventura Sander M. Houten 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(9):1467-1474
Fatty acid β-oxidation may occur in both mitochondria and peroxisomes. While peroxisomes oxidize specific carboxylic acids such as very long-chain fatty acids, branched-chain fatty acids, bile acids, and fatty dicarboxylic acids, mitochondria oxidize long-, medium-, and short-chain fatty acids. Oxidation of long-chain substrates requires the carnitine shuttle for mitochondrial access but medium-chain fatty acid oxidation is generally considered carnitine-independent. Using control and carnitine palmitoyltransferase 2 (CPT2)- and carnitine/acylcarnitine translocase (CACT)-deficient human fibroblasts, we investigated the oxidation of lauric acid (C12:0). Measurement of the acylcarnitine profile in the extracellular medium revealed significantly elevated levels of extracellular C10- and C12-carnitine in CPT2- and CACT-deficient fibroblasts. The accumulation of C12-carnitine indicates that lauric acid also uses the carnitine shuttle to access mitochondria. Moreover, the accumulation of extracellular C10-carnitine in CPT2- and CACT-deficient cells suggests an extramitochondrial pathway for the oxidation of lauric acid. Indeed, in the absence of peroxisomes C10-carnitine is not produced, proving that this intermediate is a product of peroxisomal β-oxidation. In conclusion, when the carnitine shuttle is impaired lauric acid is partly oxidized in peroxisomes. This peroxisomal oxidation could be a compensatory mechanism to metabolize straight medium- and long-chain fatty acids, especially in cases of mitochondrial fatty acid β-oxidation deficiency or overload. 相似文献
88.
Leandro Luiz Borges Fernanda Abreu Santana Isabel Samila Lima Castro Klever Márcio Antunes Arruda Humberto Josué de Oliveira Ramos Maurilio Alves Moreira Everaldo Gonçalves de Barros 《Molecular breeding : new strategies in plant improvement》2013,32(4):933-942
The common bean (Phaseolus vulgaris L.) is the main source of protein and an important source of minerals in several countries around the world. Angular leaf spot, caused by the fungus Pseudocercospora griseola, is one of the major diseases of the common bean. In this work, we used two-dimensional gel electrophoresis and mass spectrometry to analyze alterations in the proteome of common bean leaves challenged with an incompatible race of P. griseola. Twenty-three differentially expressed proteins were detected in leaves of cultivar AND 277 collected at 12, 24 and 48 h after inoculation. The proteins were digested with trypsin and submitted to MALDI-TOF/TOF and MicrOTOF-Q electrospray mass spectrometry. Nineteen of them were identified upon MS/MS fragmentation. Most of these proteins are involved with amino acid metabolism, terpenoid metabolism, phenylpropanoid biosynthesis, antioxidant systems, vitamin and cofactor metabolism, plant–pathogen interaction, carbohydrate metabolism, photosynthesis, or genetic information processing, showing that the interaction in this pathosystem affects different genes from various metabolic pathways and processes. 相似文献
89.
90.