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191.
Background
Sixteen, spring-born, single suckled, castrated male calves of Limousin × Holstein-Friesian and Simmental × Holstein-Friesian dams respectively, were used to investigate the effect of weaning on total leukocyte and differential counts, neutrophil functional activity, lymphocyte immunophenotypes, and acute phase protein response. Calves grazed with their dams until the end of the grazing season when they were housed in a slatted floor shed. On the day of housing, calves were assigned to a treatment, (i) abruptly weaned (W: n = 8) or (ii) non-weaned (controls) (C: n = 8). Weaned calves were housed in pens without their dams, whereas non-weaned (control) calves were housed with their dams. Blood was collected on day -7, 0 (housing), 2, 7, and 14 to determine total leukocyte and differential counts and concentration of fibrinogen and haptoglobin. Lymphocyte immunophenotypes were characterised using selected surface antigens (CD4+, CD8+, WC1+ (γδ T cells), MHC Class II+ lymphocytes), and the functional activities of neutrophils (surface expression of L-selectin (CD62L), phagocytic and oxidative burst activity) were investigated using flow cytometry. 相似文献192.
Sara S Roscioni Loes EM Kistemaker Mark H Menzen Carolina RS Elzinga Reinoud Gosens Andrew J Halayko Herman Meurs Martina Schmidt 《Respiratory research》2009,10(1):1-17
Background
Platelet-derived growth factor A (PDGF-A) signals solely through PDGF-Rα, and is required for fibroblast proliferation and transdifferentiation (fibroblast to myofibroblast conversion) during alveolar development, because pdgfa-null mice lack both myofibroblasts and alveoli. However, these PDGF-A-mediated mechanisms remain incompletely defined. At postnatal days 4 and 12 (P4 and P12), using mouse lung fibroblasts, we examined (a) how PDGF-Rα correlates with ki67 (proliferation marker) or alpha-smooth muscle actin (αSMA, myofibroblast marker) expression, and (b) whether PDGF-A directly affects αSMA or modifies stimulation by transforming growth factor beta (TGFβ).Methods
Using flow cytometry we examined PDGF-Rα, αSMA and Ki67 in mice which express green fluorescent protein (GFP) as a marker for PDGF-Rα expression. Using real-time RT-PCR we quantified αSMA mRNA in cultured Mlg neonatal mouse lung fibroblasts after treatment with PDGF-A, and/or TGFβ.Results
The intensity of GFP-fluorescence enabled us to distinguish three groups of fibroblasts which exhibited absent, lower, or higher levels of PDGF-Rα. At P4, more of the higher than lower PDGF-Rα + fibroblasts contained Ki67 (Ki67+), and Ki67+ fibroblasts predominated in the αSMA + but not the αSMA- population. By P12, Ki67+ fibroblasts comprised a minority in both the PDGF-Rα + and αSMA+ populations. At P4, most Ki67+ fibroblasts were PDGF-Rα + and αSMA- whereas at P12, most Ki67+ fibroblasts were PDGF-Rα- and αSMA-. More of the PDGF-Rα + than - fibroblasts contained αSMA at both P4 and P12. In the lung, proximate αSMA was more abundant around nuclei in cells expressing high than low levels of PDGF-Rα at both P4 and P12. Nuclear SMAD 2/3 declined from P4 to P12 in PDGF-Rα-, but not in PDGF-Rα + cells. In Mlg fibroblasts, αSMA mRNA increased after exposure to TGFβ, but declined after treatment with PDGF-A.Conclusion
During both septal eruption (P4) and elongation (P12), alveolar PDGF-Rα may enhance the propensity of fibroblasts to transdifferentiate rather than directly stimulate αSMA, which preferentially localizes to non-proliferating fibroblasts. In accordance, PDGF-Rα more dominantly influences fibroblast proliferation at P4 than at P12. In the lung, TGFβ may overshadow the antagonistic effects of PDGF-A/PDGF-Rα signaling, enhancing αSMA-abundance in PDGF-Rα-expressing fibroblasts. 相似文献193.
Kho CW Lee PY Bae KH Cho S Lee ZW Park BC Kang S Lee do H Park SG 《Biochemical and biophysical research communications》2006,348(1):25-35
Glutathione peroxidase (Gpx) is one of the most important anti-oxidant enzymes in yeast. Gpx3 is a ubiquitously expressed isoform that modulates the activities of redox-sensitive thiol proteins, particularly those involved in signal transduction pathways and protein translocation. In order to search for the interaction partners of Gpx3, we carried out immunoprecipitation/2-dimensional gel electrophoresis (IP-2DE), MALDI-TOF mass spectrometry, and a pull down assay. We found that Mxr1, a peptide methionine sulfoxide reductase, interacts with Gpx3. By reducing methionine sulfoxide to methionine, Mxr1 reverses the inactivation of proteins caused by the oxidation of critical methionine residues. Gpx3 can interact with Mxr1 through the formation of an intermolecular disulfide bond. When oxidative stress is induced by H(2)O(2), this interaction is compromised and the free Mxr1 then repairs the oxidized proteins. Our findings imply that this interaction links redox sensing machinery of Gpx3 to protein repair activity of Mxr1. Based on these results, we propose that Gpx3 functions as a redox-dependent exquisite regulator of the protein repair activity of Mxr1. 相似文献
194.
Iskratsch T Lange S Dwyer J Kho AL dos Remedios C Ehler E 《The Journal of cell biology》2010,191(6):1159-1172
Members of the formin family are important for actin filament nucleation and elongation. We have identified a novel striated muscle-specific splice variant of the formin FHOD3 that introduces a casein kinase 2 (CK2) phosphorylation site. The specific targeting of muscle FHOD3 to the myofibrils in cardiomyocytes is abolished in phosphomutants or by the inhibition of CK2. Phosphorylation of muscle FHOD3 also prevents its interaction with p62/sequestosome 1 and its recruitment to autophagosomes. Furthermore, we show that muscle FHOD3 efficiently promotes the polymerization of actin filaments in cardiomyocytes and that the down-regulation of its expression severely affects myofibril integrity. In murine and human cardiomyopathy, we observe reduced FHOD3 expression with a concomitant isoform switch and change of subcellular targeting. Collectively, our data suggest that a muscle-specific isoform of FHOD3 is required for the maintenance of the contractile structures in heart muscle and that its function is regulated by posttranslational modification. 相似文献
195.
Zhexin Wang Michael Grange Thorsten Wagner Ay Lin Kho Mathias Gautel Stefan Raunser 《Cell》2021,184(8):2135-2150.e13
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196.
Eman AE. Badr Rasha G. Mostafa Samah M. Awad Hala Marwan Hamed M. Abd El-Bary Hossam EM. Shehab Samar Ebrahim Ghanem 《Biochemistry and Biophysics Reports》2020
BackgroundMyocardial infarction (MI) is the major cause of death and disability worldwide. Many recent studies revealed the relationship between circulating irisin levels, endothelial dysfunctions and subclinical atherosclerosis in adult patients.ObjectivesThe aim of this study was to investigate the distribution of Irisin gene single nucleotide polymorphism in patients with MI and its association with other clinical and laboratory variables in these patients.Patients and methodsThis study was carried out in 100 patients with MI, and 100 healthy subjects served as controls. All studied subjects underwent laboratory investigations, including measurement of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c) high-density lipoprotein cholesterol (HDL-c), creatinine kinase-MB (CK-MB), troponin I (TnI) and genotyping of rs 3480 and rs726344 of Irisin genes using the TaqMan Allelic Discrimination assay technique.ResultsThere was a significant difference of Irisin genotypes in patients when compared to controls. By estimating odd ratio (OR) an association was found between G allele of rs 3480 and A allele of rs726344with increase the risk of developing myocardial infarction by 4.03 and 3.47 fold respectively. GG of rs 3480 carriers had significantly increased Troponin I and triglyceride levels, while GA carriers of rs726344 had significantly increased CKMB, Total cholesterol, LDLc, HDLc, troponin I and triglyceride levels compared with other genotypes.ConclusionG allele of rs 3480 and A allele of rs726344can considered as genetic risk factors for MI; these findings could have an impact on preventive strategy for myocardial infarction. 相似文献
197.
Ya-Dan Wen Hong Wang Sok-Hong Kho Suguro Rinkiko Xiong Sheng Han-Ming Shen Yi-Zhun Zhu 《PloS one》2013,8(2)
Background
Hydrogen sulfide (H2S) has been shown to have cytoprotective effects in models of hypertension, ischemia/reperfusion and Alzheimer''s disease. However, little is known about its effects or mechanisms of action in atherosclerosis. Therefore, in the current study we evaluated the pharmacological effects of H2S on antioxidant defenses and mitochondria protection against hydrogen peroxide (H2O2) induced endothelial cells damage.Methodology and Principal Findings
H2S, at non-cytotoxic levels, exerts a concentration dependent protective effect in human umbilical vein endothelial cells (HUVECs) exposed to H2O2. Analysis of ATP synthesis, mitochondrial membrane potential (ΔΨm) and cytochrome c release from mitochondria indicated that mitochondrial function was preserved by pretreatment with H2S. In contrast, in H2O2 exposed endothelial cells mitochondria appeared swollen or ruptured. In additional experiments, H2S was also found to preserve the activities and protein expressions levels of the antioxidants enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in H2O2 exposed cells. ROS and lipid peroxidation, as assessed by measuring H2DCFDA, dihydroethidium (DHE), diphenyl-l-pyrenylphosphine (DPPP) and malonaldehyde (MDA) levels, were also inhibited by H2S treatment. Interestingly, in the current model, D, L-propargylglycine (PAG), a selective inhibitor of cystathionine γ-lyase (CSE), abolished the protective effects of H2S donors.Innovation
This study is the first to show that H2S can inhibit H2O2 mediated mitochondrial dysfunction in human endothelial cells by preserving antioxidant defences.Significance
H2S may protect against atherosclerosis by preventing H2O2 induced injury to endothelial cells. These effects appear to be mediated via the preservation of mitochondrial function and by reducing the deleterious effects of oxidative stress. 相似文献198.
Heo JI Oh SJ Kho YJ Kim JH Kang HJ Park SH Kim HS Shin JY Kim MJ Kim SC Park JB Kim J Lee JY 《Molecular biology reports》2011,38(4):2785-2791
Since anti-apoptotic effect of ERK has not been elucidated clearly in DNA-damage-induced cell death, the role of ERK was examined in normal HEF cells treated with mild DNA damage using etoposide or camptothecin. ERK was activated by DNA damage in HEF cells. PD98059 increased apoptosis and reduced DNA-damage-induced p21Waf1/Cip1/Sdi level. Depletion of p21Waf1/Cip1/Sdi induced cell death and PD98059 induced additional cell death. DNA-damage-induced increase in cytoplasmic localization and phosphorylation of threonine residues of p21Waf1/Cip1/Sdi was reversed by PD98059. Thus, the results suggest that ERK pathway mediates anti-apoptotic effects through phosphorylation and cytoplasmic localization of p21Waf1/Cip1/Sdi in response to mild DNA damage. 相似文献
199.
200.