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排序方式: 共有161条查询结果,搜索用时 343 毫秒
71.
Burton EJ Mukaetova-Ladinska EB Perry RH Jaros E Barber R O'Brien JT 《Neurobiology of aging》2012,33(7):1228-1236
The objective of this study was to determine the neuropathological correlates of regional medial temporal lobe volume measures on magnetic resonance imaging (MRI) in subjects with Lewy body dementia (LBD). Twenty-three autopsy-confirmed LBD cases with an MRI scan close to death (mean 1.5 years) were studied. MRI-based volumetric measures were calculated for total intracranial volume, hippocampus, entorhinal cortex, and amygdala. Quantitative neuropathological analysis of plaques, tangles, and Lewy bodies were carried out in the same regions. Spearman's rho was used to examine correlations between MRI volumes and neuropathology measures and linear regression to assess the relationship between neuropathology and MRI volumes. A significant inverse correlation was observed between normalized amygdala volume and percent area of Lewy bodies in the amygdala (r = -0.461, p = 0.035). There were no other significant correlations between regional MRI volume and measures of neuropathology. Lewy body, but not Alzheimer's disease (AD) pathology was associated with reduced amygdala volume in pathologically-verified LBD cases but neither Lewy body nor Alzheimer's disease pathology was associated with volume loss in the hippocampus or entorhinal cortex, suggesting other neuropathological factors account for atrophy in these structures in LBD. 相似文献
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Semrin G Fishman DS Bousvaros A Zholudev A Saunders AC Correia CE Nemeth E Grand RJ Weinstein DA 《Inflammatory bowel diseases》2006,12(12):1101-1106
BACKGROUND: Anemia in patients with Crohn's disease (CD) is a common problem of multifactorial origin, including blood loss, malabsorption of iron, and anemia of inflammation. Anemia of inflammation is caused by the effects of inflammatory cytokines [predominantly interleukin-6 (IL-6)] on iron transport in enterocytes and macrophages. We sought to elucidate alterations in iron absorption in pediatric patients with active and inactive CD. METHODS: Nineteen subjects with CD (8 female, 11 male patients) were recruited between April 2003 and June 2004. After an overnight fast, serum iron and hemoglobin levels, serum markers of inflammation [IL-6, C-reactive protein (CRP), and erythrocyte sedimentation rate], and a urine sample for hepcidin assay were obtained at 8 am. Ferrous sulfate (1 mg/kg) was administered orally, followed by determination of serum iron concentrations hourly for 4 hours after the ingestion of iron. An area under the curve for iron absorption was calculated for each patient data set. RESULTS: There was a strong inverse correlation between the area under the curve and IL-6 (P = 0.002) and area under the curve and CRP levels (P = 0.04). Similarly, the difference between baseline and 2-hour serum iron level (Delta[Fe]2hr) correlated with IL-6 (P = 0.008) and CRP (P = 0.045). When cutoff values for IL-6 (>5 pg/mL) and CRP (>1.0 mg/dL) were used, urine hepcidin levels also positively correlated with IL-6 and CRP levels (P = 0.003 and 0.007, respectively). CONCLUSIONS: Subjects with active CD have impaired oral iron absorption and elevated IL-6 levels compared with subjects with inactive disease. These findings suggest that oral iron may be of limited benefit to these patients. Future study is needed to define the molecular basis for impaired iron absorption. 相似文献
74.
Gardenghi S Ramos P Marongiu MF Melchiori L Breda L Guy E Muirhead K Rao N Roy CN Andrews NC Nemeth E Follenzi A An X Mohandas N Ginzburg Y Rachmilewitz EA Giardina PJ Grady RW Rivella S 《The Journal of clinical investigation》2010,120(12):4466-4477
Excessive iron absorption is one of the main features of β-thalassemia and can lead to severe morbidity and mortality. Serial analyses of β-thalassemic mice indicate that while hemoglobin levels decrease over time, the concentration of iron in the liver, spleen, and kidneys markedly increases. Iron overload is associated with low levels of hepcidin, a peptide that regulates iron metabolism by triggering degradation of ferroportin, an iron-transport protein localized on absorptive enterocytes as well as hepatocytes and macrophages. Patients with β-thalassemia also have low hepcidin levels. These observations led us to hypothesize that more iron is absorbed in β-thalassemia than is required for erythropoiesis and that increasing the concentration of hepcidin in the body of such patients might be therapeutic, limiting iron overload. Here we demonstrate that a moderate increase in expression of hepcidin in β-thalassemic mice limits iron overload, decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia. Mice with increased hepcidin expression also demonstrated an increase in the lifespan of their red cells, reversal of ineffective erythropoiesis and splenomegaly, and an increase in total hemoglobin levels. These data led us to suggest that therapeutics that could increase hepcidin levels or act as hepcidin agonists might help treat the abnormal iron absorption in individuals with β-thalassemia and related disorders. 相似文献
75.
Patrick Eaton Thomas Lewis Johanna Kellett-Wright Aidan Flatt Sarah Urasa William Howlett Marieke Dekker Aloyce Kisoli Jane Rogathe Jessica Thornton Judith McCartney Vanessa Yarwood Charlotte Irwin Elizabeta B. Mukaetova-Ladinska Rufus Akinyemi William K. Gray Richard W. Walker Catherine L. Dotchin Philip C. Makupa Andrew-Leon S. Quaker Stella-Maria Paddick 《International journal of geriatric psychiatry》2020,35(10):1198-1208
76.
A phase 2 study of dalantercept,an activin receptor‐like kinase‐1 ligand trap,in patients with recurrent or metastatic squamous cell carcinoma of the head and neck 下载免费PDF全文
Antonio Jimeno MD PhD Marshall R. Posner MD Lori J. Wirth MD Nabil F. Saba MD Roger B. Cohen MD Elizabeta C. Popa MD Athanassios Argiris MD Kenneth F. Grossmann MD PhD Ammar Sukari MD Dawn Wilson Xiaosha Zhang Jade Sun Chad Glasser PharmD MPH Kenneth M. Attie MD Matthew L. Sherman MD Susan S. Pandya MD Jared Weiss MD 《Cancer》2016,122(23):3641-3649
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Preza GC Ruchala P Pinon R Ramos E Qiao B Peralta MA Sharma S Waring A Ganz T Nemeth E 《The Journal of clinical investigation》2011,121(12):4880-4888
Iron overload is the hallmark of hereditary hemochromatosis and a complication of iron-loading anemias such as β-thalassemia. Treatment can be burdensome and have significant side effects, and new therapeutic options are needed. Iron overload in hereditary hemochromatosis and β-thalassemia intermedia is caused by hepcidin deficiency. Although transgenic hepcidin replacement in mouse models of these diseases prevents iron overload or decreases its potential toxicity, natural hepcidin is prohibitively expensive for human application and has unfavorable pharmacologic properties. Here, we report the rational design of hepcidin agonists based on the mutagenesis of hepcidin and the hepcidin-binding region of ferroportin and computer modeling of their docking. We identified specific hydrophobic/aromatic residues required for hepcidin-ferroportin binding and obtained evidence in vitro that a thiol-disulfide interaction between ferroportin C326 and the hepcidin disulfide cage may stabilize binding. Guided by this model, we showed that 7–9 N-terminal amino acids of hepcidin, including a single thiol cysteine, comprised the minimal structure that retained hepcidin activity, as shown by the induction of ferroportin degradation in reporter cells. Further modifications to increase resistance to proteolysis and oral bioavailability yielded minihepcidins that, after parenteral or oral administration to mice, lowered serum iron levels comparably to those after parenteral native hepcidin. Moreover, liver iron concentrations were lower in mice chronically treated with minihepcidins than those in mice treated with solvent alone. Minihepcidins may be useful for the treatment of iron overload disorders. 相似文献