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31.
High-dose induction chemotherapy with cyclophosphamide, etoposide, and cisplatin for extensive-stage small-cell lung cancer 总被引:1,自引:0,他引:1
D H Johnson M J DeLeo K R Hande S N Wolff J D Hainsworth F A Greco 《Journal of clinical oncology》1987,5(5):703-709
To exploit possible dose-response and combination drug synergism, 20 previously untreated patients with extensive-stage small-cell lung cancer (SCLC) received one or two courses of high-dose induction chemotherapy consisting of cyclophosphamide (100 mg/kg), etoposide (1,200 mg/m2), and cisplatin (120 mg/m2) (HDCEP). HDCEP was followed by four cycles of standard-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1.4 mg/m2) (CAV). Response was determined after HDCEP and following CAV. Reevaluation included repeat bronchoscopy and chest computerized tomography (CT), as well as repetition of all initially abnormal studies. All patients were evaluable for response and toxicity. Overall response to HDCEP was 90%, with a complete response (CR) rate of 65% (95% confidence limits, 44% to 86%) and a partial response (PR) rate of 25% (95% confidence limits, 6% to 44%). All patients either maintained or improved their initial response while receiving CAV. Median duration of response was 6 months (range, 2 to 12 months) and median survival was 9.5 + months (range, 2 to 21 + months). All 37 courses of HDCEP were associated with leukopenia (less than 1,000/microL), 92% with thrombocytopenia (less than 20,000/microL), and 84% with fever of greater than 38.5 degrees C. Additional toxicities included bacteremia (24%), nausea and emesis (59%), mucositis (57%), diarrhea (38%), and hemorrhagic cystitis (5%). There were two treatment-related deaths due to infection. A third patient died 4 months after completing HDCEP with pulmonary fibrosis. Although response duration and median survival were not improved, HDCEP produced a high CR rate in ambulatory patients with extensive-stage SCLC. 相似文献
32.
Mitogens, such as polypeptide growth factors and phorbol ester tumor promoters, act by binding to specific receptors and inducing a pleiotropic response in cultured mammalian cells, which results in the induction of cellular proliferation. An early effect of such agents is the inhibition of binding of epidermal growth factor (EGF) to its receptor. Ultraviolet radiation has also been shown to induce a proliferative response in vivo and in vitro and to act as a tumor promoter in animal skin. We, therefore, examined the effect of ultraviolet radiation (UVB - 290-320 nm) on EGF binding to cells in culture. We found that UVB (100-300 J/m2) induced a rapid, dose-dependent inhibition of EGF binding in a mouse fibroblast cell line, which resulted from a decrease in both number and affinity of binding sites. Phosphorylation of the EGF receptor by protein kinase C (PKC) is not likely to be the mechanism for inhibition, since UVB treatment did not result in PKC activation or modulation of phorbol diester binding. 相似文献
33.
Longwave ultraviolet radiation and promotion of skin cancer 总被引:1,自引:0,他引:1
Exposure to solar ultraviolet (UV) radiation is recognized as an important cause of skin cancer. The carcinogenic effects of UV radiation have been attributed almost entirely to wavelengths in the mid-range (UVB, 290-320 nm). However, the development of potent UVB sunscreens has allowed individuals to increase the length of time that they spend sunbathing and, as a consequence, they may be exposed to massive doses of longwave UV radiation (UVA, 320-400 nm). There is now much evidence to suggest that UVA acts to promote tumors that have been initiated by UVB. This review considers possible mechanisms by which UVA promotes tumorigenesis. Evidence is presented which suggests that UVA acts through modulation of protein kinase C. 相似文献
34.
35.
Shandong Wu Susan P Weinstein Michael J DeLeo III Emily F Conant Jinbo Chen Susan M Domchek Despina Kontos 《Breast cancer research : BCR》2015,17(1)
IntroductionWe present a fully automated method for deriving quantitative measures of background parenchymal enhancement (BPE) from breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perform a preliminary evaluation of these measures to assess the effect of risk-reducing salpingo-oophorectomy (RRSO) in a cohort of breast cancer susceptibility gene 1/2 (BRCA1/2) mutation carriers.MethodsBreast DCE-MRI data from 50 BRCA1/2 carriers were retrospectively analyzed in compliance with the Health Insurance Portability and Accountability Act and with institutional review board approval. Both the absolute (| |) and relative (%) measures of BPE and fibroglandular tissue (FGT) were computed from the MRI scans acquired before and after RRSO. These pre-RRSO and post-RRSO measures were compared using paired Student’s t test. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to evaluate the performance of relative changes in the BPE and FGT measures in predicting breast cancer that developed in these women after the RRSO surgery.ResultsFor the 44 women who did not develop breast cancer after RRSO, the absolute volume of BPE and FGT had a significant decrease (P < 0.05) post-RRSO, whereas for the 6 women who developed breast cancer, there were no significant changes in these measures. Higher values in all BPE and FGT measures were also observed post-RRSO for the women who developed breast cancer, compared with women who did not. Relative changes in BPE percentage were most predictive of women who developed breast cancer after RRSO (P < 0.05), whereas combining BPE percentage and |FGT| yielded an AUC of 0.80, higher than BPE percentage (AUC = 0.78) or |FGT| (AUC = 0.66) alone (both P > 0.02).ConclusionsQuantitative measures of BPE and FGT are different before and after RRSO, and their relative changes are associated with prediction of developing breast cancer, potentially indicative of women who are more susceptible to develop breast cancer after RRSO in BRCA1/2 mutation carriers.
Electronic supplementary material
The online version of this article (doi:10.1186/s13058-015-0577-0) contains supplementary material, which is available to authorized users. 相似文献36.
37.
A fresh look at augmenter of liver regeneration in rats 总被引:36,自引:0,他引:36
38.
Kennedy AD Otto M Braughton KR Whitney AR Chen L Mathema B Mediavilla JR Byrne KA Parkins LD Tenover FC Kreiswirth BN Musser JM DeLeo FR 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(4):1327-1332
Emerging and re-emerging infectious diseases, especially those caused by drug-resistant bacteria, are a major problem worldwide. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) appeared rapidly and unexpectedly in the United States, resulting in an epidemic caused primarily by isolates classified as USA300. The evolutionary and molecular underpinnings of this epidemic are poorly understood. Specifically, it is unclear whether there has been clonal emergence of USA300 isolates or evolutionary convergence toward a hypervirulent phenotype resulting in the independent appearance of similar organisms. To definitively resolve this issue and understand the phylogeny of USA300 isolates, we used comparative whole-genome sequencing to analyze 10 USA300 patient isolates from eight states in diverse geographic regions of the United States and multiple types of human infection. Eight of 10 isolates analyzed had very few single nucleotide polymorphisms (SNPs) and thus were closely related, indicating recent diversification rather than convergence. Unexpectedly, 2 of the clonal isolates had significantly reduced mortality in a mouse sepsis model compared with the reference isolate (P = 0.0002), providing strong support to the idea that minimal genetic change in the bacterial genome can have profound effects on virulence. Taken together, our results demonstrate that there has been recent clonal expansion and diversification of a subset of isolates classified as USA300. The findings add an evolutionary dimension to the epidemiology and emergence of USA300 and suggest a similar mechanism for the pandemic occurrence and spread of penicillin-resistant S. aureus (known as phage-type 80/81 S. aureus) in the 1950s. 相似文献
39.
Human immunodeficiency virus-associated granuloma annulare 总被引:1,自引:0,他引:1
40.
A novel form of hereditary myeloperoxidase deficiency linked to endoplasmic reticulum/proteasome degradation. 总被引:4,自引:0,他引:4
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F R DeLeo M Goedken S J McCormick W M Nauseef 《The Journal of clinical investigation》1998,101(12):2900-2909
Myeloperoxidase (MPO) deficiency is a common inherited disorder linked to increased susceptibility to infection and malignancy. We identified a novel missense mutation in the MPO gene at codon 173 whereby tyrosine is replaced with cysteine (Y173C) that is associated with MPO deficiency and assessed its impact on MPO processing and targeting in transfectants expressing normal or mutant proteins. Although the precursor synthesized by cells expressing the Y173C mutation (MPOY173C) was glycosylated, associated with the molecular chaperones calreticulin and calnexin, and acquired heme, it was neither proteolytically processed to mature MPO subunits nor secreted. After prolonged association with calreticulin and calnexin in the endoplasmic reticulum, MPOY173C was degraded. Furthermore, the 20S proteasome inhibitor N-acetyl-L-leucinyl-L-leucinyl-L-norleucinyl inhibited its degradation, suggesting that the proteasome mediates proteolysis of MPOY173C and, thus, participates in quality control in this novel form of hereditary MPO deficiency. 相似文献