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1.
Whitney S. Brandt Wanpu Yan Jian Zhou Kay See Tan Joseph Montecalvo Bernard J. Park Prasad S. Adusumilli James Huang Matthew J. Bott Valerie W. Rusch Daniela Molena William D. Travis Mark G. Kris Jamie E. Chaft David R. Jones 《The Journal of thoracic and cardiovascular surgery》2019,157(2):743-753.e3
Objective
Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.Methods
Patients with cT2-4N0-1M0 non–small cell lung cancer who received platinum-based chemotherapy were retrospectively identified. Exclusion criteria included stage IV disease, induction radiotherapy, and targeted therapy. The primary end point was disease-free survival. Secondary end points were overall survival, chemotherapy tolerance, and ability of Response Evaluation Criteria In Solid Tumors response to predict survival. Survival was estimated using the Kaplan–Meier method, compared using the log-rank test and Cox proportional hazards models, and stratified using matched pairs after propensity score matching.Results
In total, 330 patients met the inclusion criteria (n = 92/group after propensity-score matching; median follow-up, 42 months). Five-year disease-free survival was 49% (95% confidence interval, 39-61) for neoadjuvant chemotherapy versus 48% (95% confidence interval, 38-61) for adjuvant chemotherapy (P = .70). On multivariable analysis, disease-free survival was not associated with neoadjuvant chemotherapy or adjuvant chemotherapy (hazard ratio, 1.1; 95% confidence interval, 0.64-1.90; P = .737), nor was overall survival (hazard ratio, 1.21; 95% confidence interval, 0.63-2.30; P = .572). The neoadjuvant chemotherapy group was more likely to receive full doses and cycles of chemotherapy (P = .014/0.005) and had fewer grade 3 or greater toxicities (P = .001). Response Evaluation Criteria In Solid Tumors response to neoadjuvant chemotherapy was associated with disease-free survival (P = .035); 15% of patients receiving neoadjuvant chemotherapy (14/92) had a major pathologic response.Conclusions
Timing of chemotherapy, before or after surgery, is not associated with an improvement in overall or disease-free survival among patients with cT2-4N0-1M0 non–small cell lung cancer who undergo complete surgical resection. 相似文献2.
3.
Tae-Jin Song M.D. Ph.D. David P. Eisenberg M.D. Prasad S. Adusumilli M.D. Michael Hezel B.S. Yuman Fong M.D. 《Journal of gastrointestinal surgery》2006,10(4):532-542
The rising incidence of hepatocellular carcinoma (HCC) in western countries, along with the poor prognosis offered by present-day
treatment modalities, makes novel therapies for this disease necessary. Oncolytic herpes simplex viruses (HSV) are replication-competent
viruses that are highly effective in the treatment of a wide variety of experimental models of human malignancies. This study
seeks to investigate the effectiveness of oncolytic herpes viruses in the treatment of primary HCC cell lines. Sixteen commercially
available human HCC cell lines were studied. G207 is an attenuated, replication-competent, oncolytic HSV engineered to selectively
replicate within cancer cells. Cell lines were tested for viral sensitivity to G207 and their ability to support viral replication
using standard cytotoxicity and viral replication assays. Eleven of 16 cell lines were moderately to highly sensitive to G207
viral oncolysis. HCC cell lines additionally demonstrated the ability to support viral replication in vitro with as high as
800-fold amplification of the administered viral dose observed. G207 is cytotoxic to, and efficiently replicates within, HCC
cell lines in vitro. From these data, we suggest that oncolytic HSV therapy may have a role in the treatment of HCC, and in
vivo studies are warranted.
Presented in part at the 2005 American Hepato-Pancreato-Biliary Association Congress, Hollywood, Florida, April 14–17, 2005.
Supported by grants R01CA75461 and R01CA72632 from the National Institutes of Health, and by grant MBC-99366 from the American
Cancer Society (Yuman Fong). 相似文献
4.
Stephen F Stanziale Henrik Petrowsky Prasad S Adusumilli Leah Ben-Porat Mithat Gonen Yuman Fong 《Clinical cancer research》2004,10(9):3225-3232
PURPOSE: The antitumor efficacy of a herpes simplex virus (HSV)-1 oncolytic virus depends on the cytotoxic effect of the virus, but also on viral replication and spread within the tumor. Apoptosis is considered a defense mechanism of infected cells that minimizes the spread of viral progeny by limiting cellular production of virus. We sought to determine whether oncolytic HSV-1 infection induces apoptosis in neighboring, uninfected cells and whether manipulation of apoptosis can increase viral replication and cytotoxicity. EXPERIMENTAL DESIGN: NV1066 is an oncolytic HSV-1 mutant that contains the marker gene for enhanced green fluorescent protein. OCUM human gastric cancer cells were infected with NV1066 in vitro and inspected for apoptosis by Hoechst and terminal deoxynucleotidyltransferase-mediated nick end labeling staining and for infection by expression of green fluorescence. RESULTS: A significant increase in apoptosis was seen in cells infected by NV1066. More interestingly, a significant percentage (10%) of uninfected cells also proceeded to apoptosis. After NV1066 infection, cells were also treated with N-acetylcysteine (NAC), an inhibitor of apoptosis. By day 4 after infection, 2.7x more NV1066 was produced in cells exposed to NAC than in those not exposed to NV1066 (P = 0.04). NAC also increased tumor kill when administered with virus. CONCLUSIONS: These data suggest that NV1066 induces apoptosis in uninfected cocultured cells, potentially hindering propagation of viral progeny and concomitant tumor kill. Inhibition of apoptosis may improve the efficacy of oncolytic HSV-1 therapy. 相似文献
5.
Richard J Wong Mei-Ki Chan Zhenkun Yu Ronald A Ghossein Ivan Ngai Prasad S Adusumilli Brendon M Stiles Jatin P Shah Bhuvanesh Singh Yuman Fong 《Clinical cancer research》2004,10(13):4509-4516
PURPOSE: Oncolytic herpes simplex viruses (HSVs) may have significant antitumor effects resulting from the direct lysis of cancer cells. HSVs may also be used to express inserted transgenes to exploit additional therapeutic strategies. The ability of an interleukin (IL)-12-expressing HSV to treat squamous cell carcinoma (SCC) by inhibition of tumor angiogenesis is investigated in this study. EXPERIMENTAL DESIGN: A replication-competent, attenuated, oncolytic HSV carrying the murine IL-12 gene (NV1042), its non-cytokine-carrying analog (NV1023), or saline was used to treat established murine SCC flank tumors by intratumoral injection. The expression of secondary antiangiogenic mediators was measured. Angiogenesis inhibition was assessed by in vivo Matrigel plug assays, flank tumor subdermal vascularity, and in vitro endothelial cell tubule formation assay. RESULTS: Intratumoral injections of NV1042 (2 x 10(7) plaque-forming units) into murine SCC VII flank tumors resulted in smaller tumor volumes as compared with NV1023 or saline. IL-12 and IFN-gamma expression in tumors was 440 and 2.2 pg/mg, respectively, at 24 h after NV1042 injection, but both IL-12 and IFN-gamma were undetectable (<0.2 pg/mg) after NV1023 or saline injections. Expression of two antiangiogenesis mediators, monokine induced by IFN-gamma and IFN-inducible protein 10, was elevated after NV1042 treatment. Matrigel plug assays of NV1042-transfected SCC VII tumor cells demonstrated significantly decreased hemoglobin content and microvessel density as compared with NV1023 and PBS. Excised murine flank tumors treated with NV1042 had decreased subdermal vascularity as compared with NV1023 and PBS. Both splenocytes and IL-12 expression by NV1042 were required for in vitro inhibition of endothelial tubule formation. CONCLUSIONS: IL-12 expression by an oncolytic herpes virus enhances therapy of SCC through antiangiogenic mechanisms. Strategies combining HSV oncolysis with angiogenesis inhibition merit further investigation for potential clinical application. 相似文献
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8.
Roshell Jeyaventhan BSc Geraldine Gallen RGN Pratik Choudhary FRCP Sufyan Hussain PhD 《Diabetes, obesity & metabolism》2021,23(8):1989-1994
We report a real-world evaluation of the first commercially approved automated insulin delivery (AID) system, MiniMed 670G (670G), and open source-automated insulin delivery (OS-AID) systems. This was undertaken as a retrospective observational study in adults with type 1 diabetes using AID systems for 6 months or longer in a publicly funded health service using clinically validated data. Sixty-eight adults (38 670G, 30 OS-AID systems) were included. OS-AID system users were younger, had a shorter diabetes duration and a higher education status. OS-AID systems displayed a significantly better change in HbA1c (median −0.9% [−0.4%, −1.1%] vs. −0.1% [IQR −0.7%, 0.2%], P = .004) and time in range 3.9-10 mmol/L (mean 78.5%, SD ± 12.0% vs. 68.2% ± 14.7%, P = .024) compared with 670G. Both systems showed minimal hypoglycaemia, with OS-AID systems revealing significantly improved secondary outcomes of mean glucose and percentage of time more than 10 mmol/L, with a higher percentage of time of less than 3 mmol/L. OS-AID system users displayed improved glycaemic outcomes with no clinical safety concerns compared with 670G, although higher weight-adjusted insulin dose and weight gain were noted. The study highlights key differences in OS-AID system user characteristics that are important for interpreting real-world findings from recent OS-AID system studies. 相似文献
9.
Advances in technology allowing improved insulin delivery and glucose monitoring can significantly reduce the burden of hypoglycaemia when used appropriately. However, limitations of the current technology, and the skills, commitment and motivation required to use them, mean that it does not work for all people. Education and informed professional support are key to success. In the context of problematic hypoglycaemia, data suggest that newer technology has lower efficacy and uptake in those with most need. Identifying the causes of hypoglycaemia and understanding some of the underlying behavioural drivers may prove useful and psycho-educational strategies may be effective in selected individuals. Ultimately, as in many spheres of medicine, successful management of problematic hypoglycaemia depends upon matching the right treatment to the right individual. 相似文献
10.