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141.
High-affinity antibodies to ssDNA are produced by CD-B cells in systemic lupus erythematosus patients 总被引:6,自引:0,他引:6
P Casali S E Burastero J E Balow A L Notkins 《Journal of immunology (Baltimore, Md. : 1950)》1989,143(11):3476-3483
It was previously shown that human CD5+B cells are committed to the production of polyreactive "autoantibodies" that bind different self-Ag, including ssDNA, IgG Fc fragment, thyroglobulin, and insulin, as well as exogenous Ag, e.g., tetanus toxoid and other bacterial components. To define the contribution of the CD5+B cell subset to the production of antibodies to ssDNA in SLE, we quantitated, purified, and functionally characterized circulating CD5+ and CD5-B cells in patients and in healthy subjects. We found that in SLE patients circulating CD5+B cells were not increased in number, and both CD5+ and C5-B cells spontaneously secreted antibodies to ssDNA. Studies of the mAb we generated using CD5+ and CD5-B cells revealed that two types of antibody to ssDNA are produced in SLE. The first type, of the IgM class, is produced mainly by CD5+B cells and displays a moderate affinity for ssDNA (Kd, 10(-6) to 10(-7) mol/liter) and is polyreactive, not dissimilar to the autoantibodies inducible in the normal human B cell repertoire by polyclonal activation. The second type, mostly of the IgG and IgA class, is produced mainly by CD5-B cells and displays a higher affinity (Kd, 10(-8) mol/liter) for and reacts only with ssDNA. The functional features of the high affinity anti-ssDNA antibodies and the phenotype of their producing B cells mimic those characteristic of a "mature" Ag-driven response, such as that to tetanus toxoid in tetanus toxoid-vaccinated subjects. 相似文献
142.
L. Masotti E. Casali N. Gesmundo G. Sartor P. Cavatorta S. Borrello T. Galeotti 《Cell biochemistry and biophysics》1989,14(1):53-65
Smooth and rough endoplasmic reticulum of two Morris hepatomas, the slow growing 9618A and the fast growing 3924A, have been
isolated, and their biochemical composition, supramolecular organization, and response to the action of peroxidative agents
have been studied. Cytochrome P450 content and lipid availability are the limiting factors of their peroxidizability. The hemoprotein content is reduced about
80% in hepatoma 9618A and is virtually absent in hepatoma 3924A. The peroxidizability decreases with increasing growth rate
of the tumor.
The protein, phospholipid, and cholesterol content, the fatty acid composition as well as the double bond index, and the saturated
and unsaturated fatty acid content are reported. Differences have been found between normal liver and tumors and between the
fractions within a given tumoral tissue.
The molecular order, as determined by fluorescence anisotrophy decay of DPH, increases in total microsomes and in the smooth
fraction going from liver 9618A to 3924A, whereas for the rough fraction it is the same in liver and hepatoma 9618A; in 3924A
it increases of about 30%. Fluidity decreases in total microsomes going from liver to 3924A, to 9618A. In both the purified
fractions it decreases with increasing deviation of the tumor. 相似文献
143.
L Ferreri-Santi C Agostacchio C Rosellini A M Casali M Percario P Visconti S Carlone S Parodi G Allavena 《Bollettino della Società italiana di biologia sperimentale》1990,66(4):373-380
Vitamin A is known to be able to modulate cell growth and differentiation and to act as an inhibitor of the process of carcinogenesis in some experimental models. Here we have studied the effect of different concentrations of vitamin A on chemotactic and chemoinvasive behaviour of a metastatic osteosarcoma cell line. The cell proliferation was partially inhibited in the presence of 10(-5) M retinol after 4 days of incubation. Retinol effect on chemotactic and chemoinvasive activity of osteosarcoma cells seemed to be dose-dependent. The highest retinol concentration used (10(-5) M) had an inhibitory effect on migratory and invasive cell response. Lower retinol concentrations seemed to be able to enhance (10(-8) M) both chemotactic and chemoinvasive activity of osteosarcoma cells. Chemotaxis and chemoinvasion assays provide rapid and quantitative tools to study the "in vitro" behaviour of metastatic cells. Furthermore, they represent a mean to screen for drugs, hormones and other substances able to alter the metastatic phenotype. 相似文献
144.
Ferri A Nencini M Battistini S Giannini F Siciliano G Casali C Damiano MG Ceroni M Chiò A Rotilio G Carrì MT 《Journal of neurochemistry》2004,90(5):1237-1242
Calcineurin (CaN) is a Ser/Thr protein phosphatase involved in a wide range of cellular responses to calcium mobilizing signals. Previous evidence supports the notion that calcineurin is oxidatively inhibited by mutant Cu, Zn superoxide dismutase (SOD1) typical of familial ALS patients in vitro and in transgenic mice. We report that calcineurin activity is markedly inhibited in lymphocytes from 37 sporadic, eight familial ALS patients and an asymptomatic subject carrying an SOD1 mutation as compared to 28 healthy controls. Two other healthy subjects, heterozygous for the D90A mutation from a recessive pedigree, have normal calcineurin activity. Immunoreactive CaN protein, age, sex and riluzole treatment are not related to calcineurin activity in samples from patients. However, we have observed a marked increase in total protein oxidation in extracts from ALS lymphocytes, as compared to extracts from control subjects. These data confirm that modification of calcineurin activity and possibly of calcineurin-mediated pathways of signal transduction (including modulation of apoptotic neuronal death) may contribute to the pathogenesis of ALS. 相似文献
145.
146.
Elisa Boschetti Roberto D’Alessandro Francesca Bianco Valerio Carelli Giovanna Cenacchi Antonio D. Pinna Massimo Del Gaudio Rita Rinaldi Vincenzo Stanghellini Loris Pironi Kerry Rhoden Vitaliano Tugnoli Carlo Casali Roberto De Giorgio 《PloS one》2014,9(5)
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive mitochondrial disease associated with mutations in the nuclear TYMP gene. As a result, the thymidine phosphorylase (TP) enzyme activity is markedly reduced leading to toxic accumulation of thymidine and therefore altered mitochondrial DNA. MNGIE is characterized by severe gastrointestinal dysmotility, neurological impairment, reduced life expectancy and poor quality of life. There are limited therapeutic options for MNGIE. In the attempt to restore TP activity, allogenic hematopoietic stem cell transplantation has been used as cellular source of TP. The results of this approach on ∼20 MNGIE patients showed gastrointestinal and neurological improvement, although the 5-year mortality rate is about 70%. In this study we tested whether the liver may serve as an alternative source of TP. We investigated 11 patients (7M; 35–55 years) who underwent hepatic resection for focal disorders. Margins of normal liver tissue were processed to identify, quantify and localize the TP protein by Western Blot, ELISA, and immunohistochemistry, and to evaluate TYMP mRNA expression by qPCR. Western Blot identified TP in liver with a TP/GAPDH ratio of 0.9±0.5. ELISA estimated TP content as 0.5±0.07 ng/μg of total protein. TP was identified in both nuclei and cytoplasm of hepatocytes and sinusoidal lining cells. Finally, TYMP mRNA was expressed in the liver. Overall, our study demonstrates that the liver is an important source of TP. Orthotopic liver transplantation may be considered as a therapeutic alternative for MNGIE patients. 相似文献
147.
Maternally inherited cardiomyopathy and hearing loss associated with a novel mutation in the mitochondrial tRNA(Lys) gene (G8363A). 总被引:4,自引:0,他引:4
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F. M. Santorelli S. C. Mak M. El-Schahawi C. Casali S. Shanske T. Z. Baram R. E. Madrid S. DiMauro 《American journal of human genetics》1996,58(5):933-939
A novel G8363A mutation in the mtDNA tRNA(Lys) gene was associated, in two unrelated families, with a syndrome consisting of encephalomyopathy, sensorineural hearing loss, and hypertrophic cardiomyopathy. Muscle biopsies from the probands showed mitochondrial proliferation and partial defects of complexes I, III, and IV of the electron-transport chain. The G8363A mutation was very abundant (>95%) in muscle samples from the probands and was less copious in blood from 18 maternal relatives (mean 81.3% +/- 8.5%). Single-muscle-fiber analysis showed significantly higher levels of mutant genomes in cytochrome (c) oxidase-negative fibers than in cytochrome (c) oxidase-positive fibers. The mutation was not found in >200 individuals, including normal controls and patients with other mitochondrial encephalomyopathies, thus fulfilling accepted criteria for pathogenicity. 相似文献
148.
Prenatal maternal psychological distress increases risk for adverse infant outcomes. However, the biological mechanisms underlying this association remain unclear. Prenatal stress can impact fetal epigenetic regulation that could underlie changes in infant stress responses. It has been suggested that maternal glucocorticoids may mediate this epigenetic effect. We examined this hypothesis by determining the impact of maternal cortisol and depressive symptoms during pregnancy on infant NR3C1 and BDNF DNA methylation. Fifty-seven pregnant women were recruited during the second or third trimester. Participants self-reported depressive symptoms and salivary cortisol samples were collected diurnally and in response to a stressor. Buccal swabs for DNA extraction and DNA methylation analysis were collected from each infant at 2 months of age, and mothers were assessed for postnatal depressive symptoms. Prenatal depressive symptoms significantly predicted increased NR3C1 1F DNA methylation in male infants (β = 2.147, P = 0.044). Prenatal depressive symptoms also significantly predicted decreased BDNF IV DNA methylation in both male and female infants (β = −3.244, P = 0.013). No measure of maternal cortisol during pregnancy predicted infant NR3C1 1F or BDNF promoter IV DNA methylation. Our findings highlight the susceptibility of males to changes in NR3C1 DNA methylation and present novel evidence for altered BDNF IV DNA methylation in response to maternal depression during pregnancy. The lack of association between maternal cortisol and infant DNA methylation suggests that effects of maternal depression may not be mediated directly by glucocorticoids. Future studies should consider other potential mediating mechanisms in the link between maternal mood and infant outcomes. 相似文献
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150.