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101.
Rogers IS Banerji D Siegel EL Truong QA Ghoshhajra BB Irlbeck T Abbara S Gupta R Benenstein RJ Choy G Avery LL Novelline RA Bamberg F Brady TJ Nagurney JT Hoffmann U 《The American journal of cardiology》2011,(5):163-650
Newer cardiac computed tomographic (CT) technology has permitted comprehensive cardiothoracic evaluations for coronary artery disease, pulmonary embolism, and aortic dissection within a single breath hold, independent of the heart rate. We conducted a randomized diagnostic trial to compare the efficiency of a comprehensive cardiothoracic CT examination in the evaluation of patients presenting to the emergency department with undifferentiated acute chest discomfort or dyspnea. We randomized the emergency department patients clinically scheduled to undergo a dedicated CT protocol to assess coronary artery disease, pulmonary embolism, or aortic dissection to either the planned dedicated CT protocol or a comprehensive cardiothoracic CT protocol. All CT examinations were performed using a 64-slice dual source CT scanner. The CT results were immediately communicated to the emergency department providers, who directed further management at their discretion. The subjects were then followed for the remainder of their hospitalization and for 30 days after hospitalization. Overall, 59 patients (mean age 51.2 ± 11.4 years, 72.9% men) were randomized to either dedicated (n = 30) or comprehensive (n = 29) CT scanning. No significant difference was found in the median length of stay (7.6 vs 8.2 hours, p = 0.79), rate of hospital discharge without additional imaging (70% vs 69%, p = 0.99), median interval to exclusion of an acute event (5.2 vs 6.5 hours, p = 0.64), costs of care (p = 0.16), or the number of revisits (p = 0.13) between the dedicated and comprehensive arms, respectively. In addition, radiation exposure (11.3 mSv vs 12.8 mSv, p = 0.16) and the frequency of incidental findings requiring follow-up (24.1% vs 33.3%, p = 0.57) were similar between the 2 arms. Comprehensive cardiothoracic CT scanning was feasible, with a similar diagnostic yield to dedicated protocols. However, it did not reduce the length of stay, rate of subsequent testing, or costs. In conclusion, although this "triple rule out" protocol might be helpful in the evaluation of select patients, these findings suggest that it should not be used routinely with the expectation that it will improve efficiency or reduce resource use. 相似文献
102.
Sanaa M. Kamal Amany Ahmed Sara Mahmoud Leila Nabegh Iman El Gohary Isi Obadan Tamer Hafez Dahlia Ghoraba Ahmed A. Aziz Mona Metaoei 《Liver international》2011,31(3):401-411
Aim: The therapy of chronic hepatitis C genotype 4 (HCV‐4) has not been optimized yet. This randomized, prospective, parallel‐group clinical trial compared the efficacy and safety of pegylated interferon α‐2a (PEG‐IFN α‐2a) plus ribavirin and PEG‐IFN α‐2b plus ribavirin and assessed the health‐related quality of life (HRQOL) in patients with chronic HCV‐4. Methods: Eligible patients with proven chronic HCV‐4 were randomized to receive either a weekly dose of PEG‐IFN α‐2a (180 μg) or PEG‐IFN α‐2b (1.5 μg/kg) and a daily dose of ribavirin (1000–1200 mg) for 48 weeks with 24 weeks post‐treatment follow‐up. The primary end point was sustained virological response (SVR) defined by undetectable HCV RNA 24 weeks after treatment. The Short form‐36 Health Survey version 2 (SF‐36v2) and the Chronic Liver Disease questionnaires (CLDQ) were assessed before, during and after therapy. Results: The overall SVR rate of the entire cohort was 59.9%. The SVR rates were significantly higher in patients treated with PEG‐IFN α‐2a and ribavirin (Group A; n=109) compared with those treated with PEG‐IFN α‐2b and ribavirin (Group B; n=108, 70.6 vs. 54.6%, respectively; P=0.017). The relapse rates were 5.1% for PEG‐IFN α‐2a and 15.7% for PEG‐IFN α‐2b (P=0.0019). The SF‐36v2 and CLDQ were low during therapy and improved significantly after therapy successful therapy. Conclusion: Pegylated interferon α‐2a plus ribavirin was significantly more effective than PEG‐IFN α‐2b and ribavirin therapy in the treatment of chronic HCV‐4 patients. The tolerability and adverse events were comparable between the two regimens. The HRQOL improved significantly after successful PEG‐IFN α‐2a plus ribavirin therapy. 相似文献
103.
Banerji D Martinez F Abbara S Truong QA 《Journal of Cardiovascular Computed Tomography》2011,5(3):189-191
We report the case of a 6 year old girl with Turner syndrome and aberrant right subclavian artery with an incidental finding of PAPVR on contrast-enhanced, high-pitch, 128-slice, electrocardiographic-gated dual source CT. There is value of using high-pitch DSCT in pediatric patients for diagnostic images with minimal radiation exposure. 相似文献
104.
Besmer DM Curry JM Roy LD Tinder TL Sahraei M Schettini J Hwang SI Lee YY Gendler SJ Mukherjee P 《Cancer research》2011,71(13):4432-4442
MUC1 is overexpressed and aberrantly glycosylated in more than 60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In this study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared with both KC and KCM. Cell lines derived from KCKO tumors have significantly less tumorigenic capacity compared with cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared with mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor, platelet-derived growth factor, or matrix metalloproteinase 9. Further, significantly less KCKO cells entered the G(2)-M phase of the cell cycle compared with the KCM cells. Proteomics and Western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of mitogen-activated protein kinase (MAPK), as well as a significant decrease in nestin and tubulin-α2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro. 相似文献
105.
Angiogenesis inhibition, long studied in the treatment of malignancies, has begun to emerge as a potential therapeutic approach in managing inflammatory arthritis, particularly rheumatoid arthritis. The growth of new vessels is required for the development of the rheumatoid pannus, which then leads to extensive synovial inflammation and joint destruction. Vascular endothelial growth factor is the best studied mediator of angiogenesis, and several therapies have been developed that specifically target this molecule. Several other angiogenesis mediators, such as the angiopoietin-TIE system, hypoxia inducible factor and integrin alpha(V)beta(3), as well as naturally occurring inhibitors of angiogenesis, are also being investigated as potential therapeutic targets. Additionally, there are a number of drugs, including paclitaxel, 2-methoxyestradiol and fumagillin analogs, that might have a role in inhibiting angiogenesis and, thus, in treating proliferative synovitis. 相似文献
106.
107.
A neurotrophin axis in myeloma: TrkB and BDNF promote tumor-cell survival 总被引:10,自引:0,他引:10 下载免费PDF全文
Multiple myeloma (MM) is a B-cell neoplasm that is characterized by the clonal expansion of malignant plasma cells and is frequently associated with chromosomal translocations placing an oncogene under the control of the immunoglobulin heavy chain enhancer. Despite these pathogenic translocations, MM cells remain dependent on external cues for survival. We present evidence that brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of growth factors, and its high-affinity receptor, tropomyosin receptor kinase B (TrkB), contribute to these survival cues. MM cells express TrkB, and respond to BDNF by activating mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase-a PI3K target (PI3K/Akt) signaling cascades. Addition of BDNF protects human MM cell lines (HMCLs) from apoptosis induced by dexamethasone or bortezomib and prolongs the survival of primary MM cells cultured alone or with human bone marrow (BM) stroma. As BDNF and TrkB are expressed by osteoblasts, stromal cells, and endothelial cells within the BM microenvironment, a BDNF-TrkB axis may be critical to the interactions of MM with bone and stroma that contribute to MM tumor progression. Finally, BDNF is expressed by malignant plasma cells isolated from a subset of patients with MM, as well as by most HMCLs, suggesting a potential role for this neurotrophin axis in autocrine as well as paracrine support of MM. 相似文献
108.
Sharon D Jancke D Chavane F Na'aman S Grinvald A 《Cerebral cortex (New York, N.Y. : 1991)》2007,17(12):2866-2877
Little is known about the "inverse" of the receptive field--the region of cortical space whose spatiotemporal pattern of electrical activity is influenced by a given sensory stimulus. We refer to this activated area as the cortical response field, the properties of which remain unexplored. Here, the dynamics of cortical response fields evoked in visual cortex by small, local drifting-oriented gratings were explored using voltage-sensitive dyes. We found that the cortical response field was often characterized by a plateau of activity, beyond the rim of which activity diminished quickly. Plateau rim location was largely independent of stimulus orientation. However, approximately 20 ms following plateau onset, 1-3 peaks emerged on it and were amplified for 25 ms. Spiking was limited to the peak zones, whose location strongly depended on stimulus orientation. Thus, alongside selective amplification of a spatially restricted suprathreshold response, wider activation to just below threshold encompasses all orientation domains within a well-defined retinotopic vicinity of the current stimulus, priming the cortex for processing of subsequent stimuli. 相似文献
109.
110.
David Hessl Flora Tassone Danuta Z Loesch Elizabeth Berry-Kravis Maureen A Leehey Louise W Gane Ingrid Barbato Cathlin Rice Emma Gould Deborah A Hall James Grigsby Jacob A Wegelin Susan Harris Foster Lewin Dahlia Weinberg Paul J Hagerman Randi J Hagerman 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2005,(1):115-121
Until recently, individuals with premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene were believed to be psychologically unaffected. However, the recent documentation of abnormal elevation of FMR1 mRNA, discovery of fragile X-associated tremor/ataxia syndrome (FXTAS), and reports of psychiatric disorders in children and adults with the premutation have suggested a pathogenic gene-brain-behavior mechanism. In a large collaborative study, 68 men and 144 women with the FMR1 premutation completed a psychological symptoms checklist and FMR1 genetic testing, including determination of CGG repeat size, percentage of FMR1 protein (FMRP)-positive lymphocytes, and FMR1 mRNA levels. Relative to published norms, men and women with FXTAS symptoms reported higher levels of several types of psychological symptoms. In addition, men and women with the premutation and no overt evidence of FXTAS reported higher levels of obsessive-compulsive symptoms. Elevated FMR1 mRNA, but not CGG repeat size or reduced FMRP (as measured by immunocytochemistry), was significantly associated with increased psychological symptoms, predominantly obsessive-compulsive symptoms and psychoticism, in premutation men with and without FXTAS symptoms. There was no relationship between CGG repeat size, FMR1 mRNA or FMRP and psychological symptoms in premutation women unless the sample was restricted to those with skewed X-activation ratio toward >50% active premutation alleles. The results of this study support the hypothesis that FMR1 function is associated with psychological difficulties in individuals with the premutation, and provide evidence concordant with an RNA toxic gain-of-function model in a neuropsychiatric phenotype. 相似文献