全文获取类型
收费全文 | 189篇 |
免费 | 20篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 6篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 12篇 |
2015年 | 13篇 |
2014年 | 8篇 |
2013年 | 3篇 |
2012年 | 11篇 |
2011年 | 6篇 |
2010年 | 10篇 |
2009年 | 5篇 |
2008年 | 6篇 |
2007年 | 4篇 |
2006年 | 7篇 |
2005年 | 5篇 |
2004年 | 5篇 |
2003年 | 4篇 |
2002年 | 4篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 7篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 10篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1969年 | 1篇 |
1968年 | 3篇 |
1967年 | 2篇 |
排序方式: 共有209条查询结果,搜索用时 31 毫秒
71.
The objective of this investigation was to determine whether nonmammalian myelin basic protein contained charge isomers resulting from extensive posttranslational modifications as seen in mammalian MBP. Four charge isomer components from dogfish MBP have been isolated. These forms arise by phosphorylation and deamidation modifications. Components C1, C2 and C3 have been characterized. We are currently characterizing component C8. Dogfish MBP is less cationic than mammalian MBP and has about 50% lower mobility on a basic pH gel electrophoresis relative to human and to bovine MBP. The mammalian component C1, which is unmodified, is modified in the dogfish by phosphorylation. The reduced electrophoretic mobility is largely attributable to the charge reduction resulting from phosphorylation in serine 72, 83, and 120 or 121 in C1, and C3. In component C2, two or three phosphate groups were distributed among residues 134, 138 and 139. It was found that dogfish amino acid residue 30 was a lysine residue and not a glutamate residue as reported in the literature. 相似文献
72.
Heats of solution for myelin basic protein have been determined using microcalorimetry. All aqueous systems studied yielded negative heats of solution; in contrast, trifluoroethanol produced a small positive heat of solution, while reaction with dimethyl sulfoxide was strikingly exothermic. The heat of interaction for native myelin basic protein with 8 M urea at pH 4.0, 29 degrees C, was found to be -79 +/- 16 kcal/mol. The significance of these results in terms of the protein's structural organization is discussed. 相似文献
73.
Greiciane MS Florim Heloisa C Caldas Julio CR de Melo Maria Alice SF Baptista Ida MM Fernandes Marcela Savoldi-Barbosa Gustavo H Goldman Mario Abbud-Filho 《Arthritis research & therapy》2015,17(1)
IntroductionMicrochimeric male fetal cells (MFCs) have been associated with systemic lupus erythematosus, and published studies have further correlated MFC with lupus nephritis (LN). In the present study, we evaluated the frequency of MFC in the renal tissue of patients with LN.MethodsTwenty-seven renal biopsies were evaluated: Fourteen were from women with clinical and laboratory findings of LN, and thirteen were from controls. Genomic DNA was extracted from kidney biopsies, and the male fetal DNA was quantified using real-time quantitative polymerase chain reactions for the detection of specific Y chromosome sequences.ResultsMFCs were detected in 9 (64%) of 14 of patients with LN, whereas no MFCs were found in the control group (P = 0.0006). No differences in pregnancy history were found between patients with LN and the control group. Significantly higher amounts of MFCs were found in patients with LN with serum creatinine ≤1.5 mg/dl. Furthermore, women with MFCs had significantly better renal function at the time of biopsy (P = 0.03). In contrast, patients with LN without MFCs presented with more severe forms of glomerulonephritis (World Health Organization class IV = 60% and class V = 40%).ConclusionsOur data indicate a high prevalence of MFCs in renal biopsy specimens from women with LN, suggesting a role for MFCs in the etiology of LN. The present report also provides some evidence that MFCs could have a beneficial effect in this disease.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0615-4) contains supplementary material, which is available to authorized users. 相似文献74.
Tobias Goldmann Nicolas Zeller Jenni Raasch Katrin Kierdorf Kathrin Frenzel Lars Ketscher Anja Basters Ori Staszewski Stefanie M Brendecke Alena Spiess Tuan Leng Tay Clemens Kreutz Jens Timmer Grazia MS Mancini Thomas Blank Günter Fritz Knut Biber Roland Lang Danielle Malo Doron Merkler Mathias Heikenwälder Marco Prinz 《The EMBO journal》2015,34(12):1612-1629
Microglia are tissue macrophages of the central nervous system (CNS) that control tissue homeostasis. Microglia dysregulation is thought to be causal for a group of neuropsychiatric, neurodegenerative and neuroinflammatory diseases, called “microgliopathies”. However, how the intracellular stimulation machinery in microglia is controlled is poorly understood. Here, we identified the ubiquitin‐specific protease (Usp) 18 in white matter microglia that essentially contributes to microglial quiescence. We further found that microglial Usp18 negatively regulates the activation of Stat1 and concomitant induction of interferon‐induced genes, thereby terminating IFN signaling. The Usp18‐mediated control was independent from its catalytic activity but instead required the interaction with Ifnar2. Additionally, the absence of Ifnar1 restored microglial activation, indicating a tonic IFN signal which needs to be negatively controlled by Usp18 under non‐diseased conditions. These results identify Usp18 as a critical negative regulator of microglia activation and demonstrate a protective role of Usp18 for microglia function by regulating the Ifnar pathway. The findings establish Usp18 as a new molecule preventing destructive microgliopathy. 相似文献
75.
Marina GM Viturino Jamil M Neto Flvia F Bajano Sueli MS Costa Alicia B Roque Gessica FS Borges Galina Ananina Priscila HH Rim Flvio M Medina Fernando F Costa Jos PC de Vasconcellos Mnica B de Melo 《Experimental biology and medicine (Maywood, N.J.)》2021,246(10):1148
This study aimed to evaluate the role of APOE polymorphisms (rs429358 and rs7412) in the risk of age-related macular degeneration in a sample of the Southeastern Brazilian population. Seven hundred and five unrelated individuals were analyzed, 334 with age-related macular degeneration (case group), and 371 without the disease (control group). In the case group, patients were further stratified according to disease phenotypes, divided into dry and wet age-related macular degeneration, and non-advanced and advanced age-related macular degeneration. APOE polymorphisms (rs429358 and rs7412) were evaluated through polymerase chain reaction and direct sequencing. In the comparison of cases vs. controls, none of the associations reached statistical significance, considering the Bonferroni-adjusted P-value, although there was a suggestive protection for the E3/E4 genotype (OR = 0.626; P-value = 0.037) and E4 carriers (OR = 0.6515; P-value = 0.047). Statistically significant protection for both the E3/E4 genotype and E4 carriers was observed in the comparisons: advanced age-related macular degeneration vs. controls (OR = 0.3665, P-value = 0.491 × 10−3 and OR = 0.4031, P-value = 0.814 × 10−3, respectively), advanced age-related macular degeneration vs. non-advanced age-related macular degeneration (OR = 0.2529, P-value = 0.659 × 10−4 and OR = 0.2692, P-value = 0.631 × 10−4, respectively). In the comparison of wet age-related macular degeneration vs. control, protection was statistically significant only for E3/E4 (OR = 0.4052, P-value = 0.001). None of the comparisons demonstrated any significant association for E2 genotypes or E2 carriers in age-related macular degeneration risk in this study. Findings suggest a protective role of the E4 haplotype in the APOE gene in the risk for advanced and wet forms of age-related macular degeneration, in a sample of the Brazilian population. To our knowledge, this is the first Brazilian study to show the association between APOE polymorphisms and age-related macular degeneration. 相似文献
76.
77.
Weifeng Xu MS Xinwei Chen MD Yexin Wang MS Baoting Fan MS Ke Guo MS Chi Yang MD Shiqi Yu MD Yichuan Pang MD Shanyong Zhang MD 《Journal of cellular physiology》2020,235(3):3022-3032
Considering the high rate of osteoclast-related diseases worldwide, research targeting osteoclast formation/function is crucial. In vitro, we demonstrated that chitooligosaccharide (CS) dramatically inhibited osteoclastogenesis as well as osteoclast function dose-dependently. CS suppressed osteoclast-specific genes expression during osteoclastogenesis. Furthermore, we found that CS attenuated receptor activator of nuclear factor kappa B ligand (RANKL)-mediated mitogen-activated protein kinase (MAPK) pathway involving p38, erk1/2, and jnk, leading to the reduced expression of c-fos and nuclear factor of activated T cells c1 (NFATc1) during osteoclast differentiation. In vivo, we found CS protected rats from periodontitis-induced alveolar bone loss by micro-computerized tomography and histological analysis. Overall, CS inhibited RANKL-induced osteoclastogenesis and ligature-induced rat periodontitis model, probably by suppressing the MAPK/c-fos/NFATc1 signaling pathway. Therefore, CS may be a safe and promising treatment for osteoclast-related diseases. 相似文献
78.
79.
80.
Elina MS Paaso Maritta S Jaakkola Aino K Rantala Timo T Hugg Jouni JK Jaakkola 《Respiratory research》2014,15(1)
BackgroundFamily history of asthma and other allergic diseases have been linked to the risk of childhood asthma previously, but little is known about their effect on the age-of-onset and persistency of asthma until young adulthood.MethodsWe assessed the effect of the family history of asthma and allergic diseases on persistent vs. transient, and early- vs. late-onset persistent asthma in The Espoo Cohort Study 1991–2011, a population-based cohort study of 1623 subjects (follow-up rate 63.2%). The determinants were any family history (any parent or sibling); maternal; paternal; siblings only; parents only; and both siblings and parents. Analyses were conducted separately for asthma and allergic diseases while taking the other disease into account as a confounding factor. The outcomes were persistent, transient, early-onset persistent (<13 years) and late-onset persistent asthma. Adjusted risk ratios (RR) were calculated applying Poisson regression. Q-statistics were used to assess heterogeneity between RRs.ResultsFamily history was associated with the different subtypes but the magnitude of effect varied quantitatively. Any family history of asthma was a stronger determinant of persistent (adjusted RR = 2.82, 95% CI 1.99-4.00) than transient asthma (1.65, 1.03-2.65) (heterogeneity: P = 0.07) and on early-onset than late-onset persistent asthma. Also any family history of allergic diseases was a stronger determinant of persistent and early-onset asthma. The impact of paternal asthma continued to young adulthood (early-onset: 3.33, 1.57-7.06 vs. late-onset 2.04, 0.75-5.52) while the influence of maternal asthma decreased with age (Early-onset 3.94, 2.11-7.36 vs. Late-onset 0.88, 0.28-2.81). Paternal allergic diseases did not follow the pattern of paternal asthma, since they showed no association with late-onset asthma. Also the effect estimates for other subtypes were lower than in other hereditary groups (persistent 1.29, 0.75-2.22 vs. transient 1.20, 0.67-2.15 and early-onset 1.86, 0.95-3.64 vs. late-onset 0.64, 0.22-1.80).ConclusionsFamily history of asthma and allergic diseases are strong determinants of asthma, but the magnitude of effect varies according to the hereditary group so that some subtypes have a stronger hereditary component, and others may be more strongly related to environmental exposures. Our results provide useful information for assessing the prognosis of asthma based on a thorough family history. 相似文献