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991.
Ock CY Kim EH Choi DJ Lee HJ Hahm KB Chung MH 《World journal of gastroenterology : WJG》2012,18(4):302-308
Reactive oxygen species (ROS) attack guanine bases in DNA easily and form 8-hydroxydeoxyguanosine (8-OHdG),which can bind to thymidine rather than cytosine,based on which,the level of 8-OHdG is gen-erally regarded as a biomarker of mutagenesis conse-quent to oxidative stress.For example,higher levels of 8-OHdG are noted in Helicobacter pylori-associated chronic atrophic gastritis as well as gastric cancer.However,we have found that exogenous 8-OHdG can paradoxically reduce ROS production,attenuate thenuclear factor-κB signaling pathway,and ameliorate the expression of proinflammatory mediators such as interleukin (IL)-1,IL-6,cyclo-oxygenase-2,and induc-ible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1,NOX organizer-1 and NOX activator-1 in vari-ous conditions of inflammation-based gastrointestinal (GI) diseases including gastritis,inflammatory bowel disease,pancreatitis,and even colitis-associated carci-nogenesis.Our recent finding that exogenous 8-OHdG was very effective in either inflammation-based or oxidative-stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdG can be a potential candidate for the treatment of inflammation-based GI diseases,as well as the pre-vention of inflammation-associated GI cancer.In this editorial review,the novel fact that exogenous 8-OHdG can be a functional molecule regulating oxidative-stress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced. 相似文献
992.
Lim JY Yoon SO Seol SY Hong SW Kim JW Choi SH Cho JY 《World journal of gastroenterology : WJG》2012,18(30):4037-4043
AIM: To investigate M2 isoform of pyruvate kinase (PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.METHODS: All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary treatment. Clinical and pathological information were obtained from the medical records. Gene expression microarray data from 60 cancer and 19 non-cancer gastric tissues were analyzed to evaluate the expression level of PKM2 mRNA. Tissue microarrays were constructed from 368 gastric cancer patients. Immunohistochemistry was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining intensity. Association between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was evaluated.RESULTS: PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients (log transformed expression level: 7.6 ± 0.65 vs 6.3 ± 0.51, P < 0.001). Moreover, differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers (log transformed expression level: 7.8 ± 0.70 vs 6.7 ± 0.71, P < 0.001). PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368 (39.1%) human gastric cancer cases. PKM2 expression was not related with stage (P = 0.811), but strongly correlated with gastric cancer differentiation (P < 0.001). Differentiated type cancers expressed more PKM2 protein than did the undifferentiated ones. Well differentiated adenocarcinoma showed 63.6% PKM2-positive cells; in contrast, signet-ring cell cancers showed only 17.7% PKM2-positive cells. Importantly, PKM2 expression was correlated with shorter overall survival (P < 0.05) independent of stage only in signet-ring cell cancers.CONCLUSION: PKM2 expression might be an adverse prognostic factor for signet-ring cell carcinomas. Its function and potential as a prognostic marker should be further verified in gastric cancer. 相似文献
993.
Song MJ Bae SH Yoo IeR Park CH Jang JW Chun HJ Choi BG Lee HG Choi JY Yoon SK 《World journal of gastroenterology : WJG》2012,18(25):3215-3222
AIM: To investigate the correlation of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) with clinical features and the prediction of treatment response.METHODS: A total of 83 hepatocellular carcinoma (HCC) patients undergoing 18F-FDG PET before transarterial chemolipiodolization with systemic chemo-infusion between October, 2006 and May, 2009 were retrospectively enrolled. The patients included 68 men and 15 women (mean age, 60 ± 10.7 years). The effect of 18F-FDG-monitored PET uptake on clinical features and on the evaluated treatment response was ascertained with modified Response Evaluation Criteria in Solid Tumors. The PET parameters of maximal standardized uptake value of the tumor (Tsuvmax), the ratio of the tumor maximal standardized uptake value (SUV) to the liver maximal SUV (Tsuvmax/Lsuvmax) and the ratio of tumor maximal SUV to the liver mean SUV (Tsuvmax/Lsuvmean) were tested as predictive factors.RESULTS: Among the 3 SUV parameters, the Tsuvmax/Lsuvmean ratio (cutoff value of 1.90) was significantly associated with tumor burden including tumor size, tumor number, α-fetoprotein levels and tumor stage (P < 0.001, P = 0.008, P = 0.011, P < 0.001, respectively). The objective response rates in patients with a high SUV ratio (≥ 1.90) were significantly better than those with a low SUV ratio (< 1.90) (P = 0.020). The overall survival rates of patients exhibiting a low Tsuvmax/Lsuvmean ratio (< 1.90) and those with a high SUV ratio (≥ 1.90) was 38.2 and 10.3 mo, respectively (P < 0.01). However, the time to progression showed no significant difference between the groups (P = 0.15).CONCLUSION: 18F-FDG PET can be an important predictor of HCC treatment. In particular, the Tsuvmax/Lsuvmean ratio (cutoff value of 1.90) can provide useful information in treatment prognosis for HCC patients treated with locoregional therapy. 相似文献
994.
Chan A Verma S Loibl S Crawford J Choi MR Dreiling L Vandenberg T 《Critical reviews in oncology/hematology》2012,81(2):136-150
In this article, we reviewed and quantified reporting of the risk of myelotoxicity, specifically febrile neutropenia (FN), and the related use of supportive care with colony-stimulating factor (CSF) or antibiotics in clinical trials published between January 2005 and June 2009, evaluating emerging regimens for the treatment of selected solid tumors. Our analysis showed that clinically significant neutropenia and neutropenia-related events were generally described in the studies evaluated (grade 3/4 neutropenia incidence, 72%; FN incidence, 53%). However, use of CSF and antibiotics was infrequently and inconsistently reported (trials reporting prophylactic CSF and antibiotics use: in the methods section, 38% and 10%, respectively; in the results section, 19% and 1%, respectively). These results highlight the need for a standardized approach to reporting neutropenic outcomes and use of supportive care measures. This can assist clinicians in prospectively managing relevant toxicities associated with these emerging regimens and thereby facilitate their safe and effective use in clinical practice. 相似文献
995.
Despite various medications for Kawasaki disease, a small number of children have been undergoing interventions for severe coronary artery complications. Transcatheter intervention is a feasible alternative to coronary artery bypass grafting in a patient with chronic totally occluded lesion after Kawasaki disease, even by stent fracture. 相似文献
996.
Shi Y Cao J Gao J Zheng L Goodwin A An CH Patel A Lee JS Duncan SR Kaminski N Pandit KV Rosas IO Choi AM Morse D 《American journal of respiratory and critical care medicine》2012,186(5):412-419
Rationale: The discovery that retinoic acid-related orphan receptor (Rora)-α is highly expressed in lungs of patients with COPD led us to hypothesize that Rora may contribute to the pathogenesis of emphysema. Objectives: To determine the role of Rora in smoke-induced emphysema. Methods: Cigarette smoke extract in vitro and elastase or cigarette smoke exposure in vivo were used to model smoke-related cell stress and airspace enlargement. Lung tissue from patients undergoing lung transplantation was examined for markers of DNA damage and Rora expression. Measurements and Main Results: Rora expression was induced by cigarette smoke in mice and in cell culture. Gene expression profiling of Rora-null mice exposed to cigarette smoke demonstrated enrichment for genes involved in DNA repair. Rora expression increased and Rora translocated to the nucleus after DNA damage. Inhibition of ataxia telangiectasia mutated decreased the induction of Rora. Gene silencing of Rora attenuated apoptotic cell death in response to cigarette smoke extract, whereas overexpression of Rora enhanced apoptosis. Rora-deficient mice were protected from elastase and cigarette smoke induced airspace enlargement. Finally, lungs of patients with COPD showed evidence of increased DNA damage even in the absence of active smoking. Conclusions: Taken together, these findings suggest that DNA damage may contribute to the pathogenesis of emphysema, and that Rora has a previously unrecognized role in cellular responses to genotoxicity. These findings provide a potential link between emphysema and features of premature ageing, including enhanced susceptibility to lung cancer. 相似文献
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1000.
Youn Ho Shin Sun Jung Jang Jung Won Yoon Hye Mi Jee Sun Hee Choi Hye Yung Yum David Warburton Man Yong Han 《Canadian respiratory journal》2012,19(4):273-277