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11.
Sebastian Dolff Daniel Quandt Benjamin Wilde Thorsten Feldkamp Fan Hua Xin Cai Christof Specker Andreas Kribben Cees GM Kallenberg Oliver Witzke 《Arthritis research & therapy》2010,12(4):R150
Introduction
There is growing evidence that interleukin 17 (IL-17) producing T cells are involved in the pathogenesis of systemic lupus erythematosus (SLE). Previous studies showed that increased percentages of T-cell subsets expressing the costimulatory molecules CD80 and CD134 are associated with disease activity and renal involvement in SLE. The aim of this study was to investigate the distribution and phenotypical characteristics of IL-17 producing T-cells in SLE, in particular in patients with lupus nephritis, with emphasis on the expression of CD80 and CD134. 相似文献12.
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Jamil M Neto Marina GM Viturino Galina Ananina Flvia F Bajano Sueli M da S Costa Alicia B Roque Gessica FS Borges Raissa Franchi Priscila HH Rim Flvio M Medina Fernando F Costa Mnica B de Melo Jos PC de Vasconcellos 《Experimental biology and medicine (Maywood, N.J.)》2021,246(21):2290
This study aimed to investigate the association among genetic variants of the complement pathway CFB R32Q (rs641153), C3 R102G (rs2230199), and CFH (rs1410996) with age-related macular degeneration (AMD) in a sample of the Brazilian population. In a case-control study, 484 AMD patients were classified according to the clinical age-related maculopathy grading system (CARMS) and compared to 479 unrelated controls. The genetic variants rs1410996 of complement H (CFH), rs641153 of complement factor B (CFB), and rs2230199 of complement 3 (C3) were evaluated through polymerase chain reaction (PCR) and direct sequencing. The associations between single nucleotide polymorphisms (SNPs) and AMD, adjusted by age, were assessed by using logistic regression models. A statistically significant association was observed between AMD risk and rs2230199 variant with an OR of 2.01 (P = 0.0002) for CG individuals compared to CC individuals. Regarding the comparison of advanced AMD versus the control group, the OR was 2.12 (P = 0.0036) for GG versus AA genotypes for rs1410996 variant. Similarly, the OR for rs2230199 polymorphism was 2.3034 (P = 5.47e-05) when comparing CG individuals to CC carriers. In contrast, the rs641153 variant showed a significant protective effect against advanced AMD for GA versus GG genotype (OR = 0.4406; P = 0.0019). When comparing wet AMD versus controls, a significant association was detected for rs1410996 variant (OR = 2.16; P = 0.0039) comparing carriers of the homozygous GG versus AA genotype, as well as in the comparisons of GG (OR = 3.0713; P = 0.0046) and CG genotypes (OR = 2.2249; P = 0.0002) versus CC genotype for rs2230199 variant, respectively. The rs641153 variant granted a significant protective effect against wet AMD for GA versus GG genotypes (OR = 0.4601; P = 0.0044). Our study confirmed the risk association between rs2230199 and rs1410996 variants and AMD, and the protective role against AMD for rs641153 variant. 相似文献
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QTL detection experiments in livestock species commonly use the half-sib design. Each male is mated to a number of females, each female producing a limited number of progeny. Analysis consists of attempting to detect associations between phenotype and genotype measured on the progeny. When family sizes are limiting experimenters may wish to incorporate as much information as possible into a single analysis. However, combining information across sires is problematic because of incomplete linkage disequilibrium between the markers and the QTL in the population. This study describes formulæ for obtaining MLEs via the expectation maximization (EM) algorithm for use in a multiple-trait, multiple-family analysis. A model specifying a QTL with only two alleles, and a common within sire error variance is assumed. Compared to single-family analyses, power can be improved up to fourfold with multi-family analyses. The accuracy and precision of QTL location estimates are also substantially improved. With small family sizes, the multi-family, multi-trait analyses reduce substantially, but not totally remove, biases in QTL effect estimates. In situations where multiple QTL alleles are segregating the multi-family analysis will average out the effects of the different QTL alleles. 相似文献
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Oxygenation measurement by multi‐wavelength oxygen‐dependent phosphorescence and delayed fluorescence: catchment depth and application in intact heart 下载免费PDF全文
Gianmarco M. Balestra Maurice C.G. Aalders Patricia A.C. Specht Can Ince Egbert G. Mik 《Journal of biophotonics》2015,8(8):615-628
Oxygen delivery and metabolism represent key factors for organ function in health and disease. We describe the optical key characteristics of a technique to comprehensively measure oxygen tension (PO2) in myocardium, using oxygen‐dependent quenching of phosphorescence and delayed fluorescence of porphyrins, by means of Monte Carlo simulations and ex vivo experiments. Oxyphor G2 (microvascular PO2) was excited at 442 nm and 632 nm and protoporphyrin IX (mitochondrial PO2) at 510 nm. This resulted in catchment depths of 161 (86) µm, 350 (307) µm and 262 (255) µm respectively, as estimated by Monte Carlo simulations and ex vivo experiments (brackets). The feasibility to detect changes in oxygenation within separate anatomical compartments is demonstrated in rat heart in vivo.
16.
Todd A. Brugel Reed W. Smith Michael Balestra Christopher Becker Thalia Daniels Gerard M. Koether Scott R. Throner Laura M. Panko Dean G. Brown Ruifeng Liu John Gordon Matthew F. Peters 《Bioorganic & medicinal chemistry letters》2010,20(18):5405-5410
Further structure activity relationship studies on a previously reported 8-azabicyclo[3.2.1]octan-3-yloxy-benzamide series of potent and selective kappa opioid receptor antagonists is discussed. Modification of the pendant N-substitution to include a cyclohexylurea moiety produced analogs with greater in vitro opioid and hERG selectivity such as 12 (κ IC50 = 172 nM, μ:κ ratio = 93, δ:κ ratio = >174, hERG IC50 = >33 μM). Changes to the linker conformation and identity as well as to the benzamide ring moiety were also investigated. 相似文献
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Chen HK Liu Z Meyer-Franke A Brodbeck J Miranda RD McGuire JG Pleiss MA Ji ZS Balestra ME Walker DW Xu Q Jeong DE Budamagunta MS Voss JC Freedman SB Weisgraber KH Huang Y Mahley RW 《The Journal of biological chemistry》2012,287(8):5253-5266
Apolipoprotein E4 (apoE4), the major genetic risk factor for late onset Alzheimer disease, assumes a pathological conformation, intramolecular domain interaction. ApoE4 domain interaction mediates the detrimental effects of apoE4, including decreased mitochondrial cytochrome c oxidase subunit 1 levels, reduced mitochondrial motility, and reduced neurite outgrowth in vitro. Mutant apoE4 (apoE4-R61T) lacks domain interaction, behaves like apoE3, and does not cause detrimental effects. To identify small molecules that inhibit domain interaction (i.e. structure correctors) and reverse the apoE4 detrimental effects, we established a high throughput cell-based FRET primary assay that determines apoE4 domain interaction and secondary cell- and function-based assays. Screening a ChemBridge library with the FRET assay identified CB9032258 (a phthalazinone derivative), which inhibits domain interaction in neuronal cells. In secondary functional assays, CB9032258 restored mitochondrial cytochrome c oxidase subunit 1 levels and rescued impairments of mitochondrial motility and neurite outgrowth in apoE4-expressing neuronal cells. These benefits were apoE4-specific and dose-dependent. Modifying CB9032258 yielded well defined structure-activity relationships and more active compounds with enhanced potencies in the FRET assay (IC(50) of 23 and 116 nm, respectively). These compounds efficiently restored functional activities of apoE4-expressing cells in secondary assays. An EPR binding assay showed that the apoE4 structure correction resulted from direct interaction of a phthalazinone. With these data, a six-feature pharmacophore model was constructed for future drug design. Our results serve as a proof of concept that pharmacological intervention with apoE4 structure correctors negates apoE4 detrimental effects in neuronal cells and could be further developed as an Alzheimer disease therapeutic. 相似文献
20.
Nadine?AME?van der BeekEmail author Juna?M?de Vries Marloes?LC?Hagemans Wim?CJ?Hop Marian?A?Kroos John?HJ?Wokke Marianne?de Visser Baziel?GM?van Engelen Jan?BM?Kuks Anneke?J?van der Kooi Nicolette?C?Notermans Karin?G?Faber Jan?JGM?Verschuuren Arnold?JJ?Reuser Ans?T?van der Ploeg Pieter?A?van Doorn 《Orphanet journal of rare diseases》2012,7(1):88