全文获取类型
收费全文 | 190篇 |
免费 | 20篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 2篇 |
2017年 | 3篇 |
2016年 | 9篇 |
2015年 | 9篇 |
2014年 | 7篇 |
2013年 | 9篇 |
2012年 | 11篇 |
2011年 | 11篇 |
2010年 | 8篇 |
2009年 | 5篇 |
2008年 | 12篇 |
2007年 | 10篇 |
2006年 | 7篇 |
2005年 | 6篇 |
2004年 | 5篇 |
2003年 | 3篇 |
2002年 | 6篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 6篇 |
1989年 | 3篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 4篇 |
1982年 | 1篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1970年 | 2篇 |
1962年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有210条查询结果,搜索用时 15 毫秒
61.
Sandra E. Gomez-Mejiba Zili Zhai Maria C. Della-Vedova Marcos D. Muñoz Saurabh Chatterjee Rheal A. Towner Kenneth Hensley Robert A. Floyd Ronald P. Mason Dario C. Ramirez 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Immuno-spin trapping (IST) is based on the reaction of a spin trap with a free radical to form a stable nitrone adduct, followed by the use of antibodies, rather than traditional electron paramagnetic resonance spectroscopy, to detect the nitrone adduct. IST has been successfully applied to mechanistic in vitro studies, and recently, macromolecule-centered radicals have been detected in models of drug-induced agranulocytosis, hepatotoxicity, cardiotoxicity, and ischemia/reperfusion, as well as in models of neurological, metabolic and immunological diseases.Scope of the review
To critically evaluate advances, challenges, and pitfalls as well as the scientific opportunities of IST as applied to the study of protein-centered free radicals generated in stressed organelles, cells, tissues and animal models of disease and exposure.Major conclusions
Because the spin trap has to be present at high enough concentrations in the microenvironment where the radical is formed, the possible effects of the spin trap on gene expression, metabolism and cell physiology have to be considered in the use of IST and in the interpretation of results. These factors have not yet been thoroughly dealt with in the literature.General significance
The identification of radicalized proteins during cell/tissue response to stressors will help define their role in the complex cellular response to stressors and pathogenesis; however, the fidelity of spin trapping/immuno-detection and the effects of the spin trap on the biological system should be considered.This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. 相似文献62.
Joyce JBC van Beers Annemiek Willemze Judith Stammen-Vogelzangs Jan W Drijfhout René EM Toes Ger J M Pruijn 《Arthritis research & therapy》2012,14(1):R35-16
Introduction
Fibronectin is one of the most abundant proteins present in the inflamed joint. Here, we characterized the citrullination of fibronectin in the joints of rheumatoid arthritis (RA) patients and studied the prevalence, epitope specificity and human leukocyte antigen (HLA) association of autoantibodies against citrullinated fibronectin in RA.Methods
Citrullinated residues in fibronectin isolated from RA patient synovial fluid were identified by mass spectrometry. The corresponding citrullinated and non-citrullinated peptides were synthesized and used to analyze the presence of autoantibodies to these peptides in RA sera and sera from other diseases and healthy controls by ELISA. The data were compared with risk factors like shared epitope HLA alleles and smoking, and with clinical features.Results
Five citrullinated residues were identified in fibronectin from RA synovial fluid. RA sera reacted in a citrulline-dependent manner with two out of four citrullinated fibronectin peptides, one of which contains two adjacent citrulline residues, in contrast to non-RA sera, which were not reactive. The most frequently recognized peptide (FN-Cit1035,1036, LTVGLTXXGQPRQY, in which × represents citrulline) was primarily targeted by anti-CCP (cyclic citrullinated peptide) 2-positive RA patients. Anti-FN-Cit1035,1036 autoantibodies were detected in 50% of established anti-CCP2-positive RA patients and in 45% of such patients from a early arthritis clinic. These antibodies appeared to be predominantly of the immunoglobulin G (IgG) isotype and to be associated with HLA shared epitope alleles (odds ratio = 2.11).Conclusions
Fibronectin in the inflamed synovia of RA patients can be citrullinated at least at five positions. Together with the flanking amino acids, three of these citrullinated residues comprise two epitopes recognized by RA autoantibodies. Anti-citrullinated fibronectin peptide antibodies are associated with HLA shared epitope alleles. 相似文献63.
Y.A. Tesiram D. Saunders R.A. Towner 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2005,1737(1):61-68
Liver cancer is one of the most common cancers worldwide. Altered lipid metabolism in the liver is a key feature of developing liver nodules and tumors. Methods of analysis vary from the most sophisticated chromatography to the in vivo nuclear magnetic resonance (NMR) spectroscopy. In this study, we present a systematic method for the identification and quantitation of signature signals from lipid metabolites using 1D NMR proton spectroscopy. We assessed lipid metabolites in an epigenetic rat hepatocarcinogenesis model induced by treatment with a choline-deficient diet (CDAA, choline-deficient l-amino acid defined) over a period of 1 year, from the formation of steatosis, to the development of nodules and adenomas. A comparable choline-sufficient (CSAA) diet was used for the controls. The resonances of the methylene protons of the glycerol backbone in phospholipids were used to quantify the total concentration of such compounds. CDAA rat livers were found to have significantly higher levels of phospholipids, when compared to CSAA, throughout the entire carcinogenesis period. The tri-methyl protons of choline compounds serves to quantify total choline, and the vinyl and bis-allyl proton resonances can be used to not only quantify fatty acid concentrations but also to probe the number of double bonds in a fatty acid moiety. Early stages of carcinogenesis indicate a lower degree of double bonds in fatty acyl containing compounds in CDAA rat livers, when compared to CSAA. The results of this study are in agreement with those previously published in the literature on other rat hepatocarcinogenesis models. 相似文献
64.
65.
Phenyl-tert-butylnitrone induces tumor regression and decreases angiogenesis in a C6 rat glioma model 总被引:2,自引:0,他引:2
Doblas S Saunders D Kshirsagar P Pye Q Oblander J Gordon B Kosanke S Floyd RA Towner RA 《Free radical biology & medicine》2008,44(1):63-72
The prognosis of patients who are diagnosed with glioblastoma multiforme is very poor, due to the difficulty of an early and accurate diagnosis and the lack of currently efficient therapeutic compounds. The efficacy of phenyl-tert-butylnitrone (PBN) as a potential anti-glioma therapeutic drug was assessed by magnetic resonance (MR) imaging (T(1)/T(2)-weighted imaging) and MR angiography (time-of-flight imaging, in conjunction with a Mathematica-based program) methods by monitoring morphologic properties, growth patterns, and angiogenic behaviors of a moderately aggressive rat C6 glioma model. MR results from untreated rats showed the diffusive invasiveness of C6 gliomas, with some associated angiogenesis. PBN administration as a pretreatment was found to clearly induce a decrease in growth rate and tumor regression as well as preventing angiogenesis. This compound even had a 40% efficiency in reducing well-established tumors. MR findings rivaled those from histology and angiogenesis marker immunostaining evaluations. In this study we demonstrated the efficiency of PBN as a potential anti-glioma drug and found it to inhibit tumor cell proliferation and prevent vascular alterations in early stages of glioma progression. The MR methods that we used also proved to be particularly suitable in following the angiogenic behavior and treatment response of a potential anti-glioma agent in a rat C6 glioma model. 相似文献
66.
Background
There is a frequent need to obtain sets of functionally equivalent homologous proteins (FEPs) from different species. While it is usually the case that orthology implies functional equivalence, this is not always true; therefore datasets of orthologous proteins are not appropriate. The information relevant to extracting FEPs is contained in databanks such as UniProtKB/Swiss-Prot and a manual analysis of these data allow FEPs to be extracted on a one-off basis. However there has been no resource allowing the easy, automatic extraction of groups of FEPs – for example, all instances of protein C. 相似文献67.
Satou Y Mineta K Ogasawara M Sasakura Y Shoguchi E Ueno K Yamada L Matsumoto J Wasserscheid J Dewar K Wiley GB Macmil SL Roe BA Zeller RW Hastings KE Lemaire P Lindquist E Endo T Hotta K Inaba K 《Genome biology》2008,9(10):R152-11
Background
The draft genome sequence of the ascidian Ciona intestinalis, along with associated gene models, has been a valuable research resource. However, recently accumulated expressed sequence tag (EST)/cDNA data have revealed numerous inconsistencies with the gene models due in part to intrinsic limitations in gene prediction programs and in part to the fragmented nature of the assembly.Results
We have prepared a less-fragmented assembly on the basis of scaffold-joining guided by paired-end EST and bacterial artificial chromosome (BAC) sequences, and BAC chromosomal in situ hybridization data. The new assembly (115.2 Mb) is similar in length to the initial assembly (116.7 Mb) but contains 1,272 (approximately 50%) fewer scaffolds. The largest scaffold in the new assembly incorporates 95 initial-assembly scaffolds. In conjunction with the new assembly, we have prepared a greatly improved global gene model set strictly correlated with the extensive currently available EST data. The total gene number (15,254) is similar to that of the initial set (15,582), but the new set includes 3,330 models at genomic sites where none were present in the initial set, and 1,779 models that represent fusions of multiple previously incomplete models. In approximately half, 5'-ends were precisely mapped using 5'-full-length ESTs, an important refinement even in otherwise unchanged models.Conclusion
Using these new resources, we identify a population of non-canonical (non-GT-AG) introns and also find that approximately 20% of Ciona genes reside in operons and that operons contain a high proportion of single-exon genes. Thus, the present dataset provides an opportunity to analyze the Ciona genome much more precisely than ever. 相似文献68.
69.
70.
Detoxification of ochratoxin A can be achieved by chemical or enzymatic hydrolyzation, the products of such reactions are ochratoxin α and phenylalanine. Ochratoxin α like ochratoxin A, is a fluorescing molecule, therefore sensitive analysis is possible at very low concentration levels. Methods have been established that make it possible to look for residues of ochratoxin A and its main metabolite ochratoxin α in blood and tissues at very low concentration levels. Plasma is extracted by the use of small amounts of chloroform; the extract is cleaned with water and afterwards evaporated to dryness]. The residue is re-dissolved and analysed by HPLC-FLD. Using this method a limit of detection of 0.5μg/l for both ochratoxin A and ochratoxin α can be reached. 相似文献