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31.
Early side effects of radiation therapy are generally the result of mitotic-linked cell death in rapidly renewing tissues and secondary impaired tissue function. Various types of acute normal tissue reactions are briefly summarized in this article. In general, with conventionally fractionated radiation treatment, the acute normal tissue reactions are within acceptable limits. However, new radiotherapy strategies, such as hyperfractionation and accelerated fractionation, induce more severe acute toxicity. Particularly, with most altered fractionation schedules, the mucosal reaction of the upper aerodigestive tract is elevated to the upper limit of tolerance. Early mucosal reactions may also become dose limiting when radiation is combined with chemotherapy as, for instance, for the treatment of head and neck cancer or pelvic neoplasms. Bone marrow is the critical organ for combination of chemotherapy and wide field irradiation. There is an increasing body of evidence that iatrogenic acute normal tissue toxicity has become a major obstacle for treatment intensification for a variety of cancers. Therefore, effective measures to ameliorate these side effects are essential for further development of cancer therapy. Methods to reduce the severity of acute toxicity are being investigated. 相似文献
32.
Hamzeh Kayhanian Emily Goode Francesco Sclafani Joo Ern Ang Marco Gerlinger David Gonzalez de Castro Scott Shepherd Clare Peckitt Sheela Rao David Watkins Ian Chau David Cunningham Naureen Starling 《Clinical colorectal cancer》2018,17(1):e69-e76
Background
Somatic v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, present in approximately 10% of metastatic colorectal cancer (mCRC) cases, is associated with poor prognosis. Patient outcome outside of clinical trials has only been reported in small series. We report real-world data on treatment and survival for BRAF-mutated (MT) patients at a single tertiary center, compared with a matched BRAF wild type (WT) control group.Patients and Methods
All colorectal cancer patients tested for BRAF mutation, from October 2010 to November 2014 were identified. BRAF-MT mCRC cases were compared with an age and sex-matched BRAF-WT control group. Clinicopathological data were collected and survival calculated using the Kaplan–Meier method and comparisons made using Cox regression.Results
Forty-three of 503 patients (8.5%) tested had BRAF-MT mCRC and were compared with 88 BRAF-WT controls. Median overall survival (mOS) was 18.2 months for BRAF-MT and 41.1 months for BRAF-WT mCRC patients (hazard ratio, 2.74; 95% confidence interval, 1.60-4.70; P < .001). Progression-free survival for BRAF-MT and WT patients, respectively, was: 8.1 months versus 9.2 months (P = .571) first-line, 5.5 months versus 8.3 months (P = .074) second-line, and 1.8 months versus 5.6 months (P = .074) third-line. Treatment using sequential fluoropyrimidine-based doublet chemotherapy was similar between both groups. Anti-epidermal growth factor receptor (EGFR) therapy was mainly given third-line with progressive disease in 90% (n = 9 of 10) of BRAF-MT patients at first restaging.Conclusion
In this case-control study, the poor mOS of BRAF-MT mCRC was associated with reduced treatment benefit beyond first-line. Sequential doublet chemotherapy remains a reasonable option in appropriately selected patients. BRAF-MT patients did not benefit from anti-EGFR therapy in this study. Recruitment to clinical trials is recommended to improve outcomes in BRAF-MT mCRC. 相似文献33.
Potentiation of tumor response to radiation or chemoradiation by selective cyclooxygenase-2 enzyme inhibitors 总被引:15,自引:0,他引:15
Nakata E Mason KA Hunter N Husain A Raju U Liao Z Ang KK Milas L 《International journal of radiation oncology, biology, physics》2004,58(2):369-375
Cyclooxygenase-2 (COX-2) is an enzyme expressed primarily in pathologic states, such as inflammatory disorders and cancer, where it mediates prostaglandin production. Its overexpression is associated with more aggressive biologic tumor behavior and adverse patient outcome. Increasing evidence shows that agents that selectively inhibit COX-2 enhance tumor response to radiation or chemotherapeutic agents. This article gives an overview of some of this evidence. In addition, we describe new results showing that celecoxib, a selective COX-2 inhibitor, enhanced response of A431 human tumor xenografts in nude mice to radiation by an enhancement factor (EF) of 1.43 and to the chemotherapeutic agent docetaxel by an EF of 2.07. Celecoxib also enhanced tumor response when added to the combined docetaxel plus radiation treatment (EF = 2.13). Further experiments showed that selective COX-2 inhibitors enhanced tumor cell sensitivity to ionizing radiation, involving inhibition of cellular repair from radiation damage and cell cycle redistribution as mechanisms for some cell types. The results show that selective COX-2 inhibitors have the potential to improve tumor radiotherapy or radiochemotherapy, and this therapeutic strategy is currently under clinical testing. 相似文献
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35.
目的 探讨乳腺癌患者心理社会适应水平现状,并分析其与生活质量的相关性,为提高乳腺癌患者生活质量提供新的方向。方法 选取2020年9月至2021年6月新疆某三甲医院就诊的264例乳腺癌患者作为研究对象,采用一般资料调查问卷、乳腺癌心理社会适应问卷、乳腺癌患者生命质量问卷进行调查,分析乳腺癌患者心理社会适应水平与生活质量的相关性。结果 乳腺癌患者心理社会适应水平得分为(147.59±17.59)分,生活质量得分为(95.83±15.04)分;相关性分析结果显示,乳腺癌患者心理社会适应水平得分与生活质量总分呈正相关(r=0.379,P<0.001);多元分层回归结果显示,心理社会适应水平进入生活质量影响因素模型,心理社会适应水平可独立解释乳腺癌生活质量14.70%的变异。结论 乳腺癌患者疾病心理社会适应处于中低水平,且与生活质量呈正相关,疾病心理社会适应水平是其生活质量的重要预测因子。 相似文献
36.
Subramanyam Vankadara Monique Danielle Dawson Jia Yi Fong Qin Yao Oh Qi An Ang Boping Liu Hong Yun Chang Judice Koh Xiaoying Koh Qian Wen Tan Joma Joy Cheng San Brian Chia 《ACS medicinal chemistry letters》2022,13(8):1345
The SARS-CoV-2 pandemic is currently causing an unprecedented global health emergency since its emergence in December 2019. In December 2021, the FDA granted emergency use authorization to nirmatrelvir, a SARS-CoV-2 main protease inhibitor, for treating infected patients. This peptidomimetic is designed with a nitrile warhead, which forms a covalent bond to the viral protease. Herein, we investigate nirmatrelvir analogs with different warheads and their inhibitory activities. In addition, antiviral activities against human alphacoronavirus 229E was also investigated along with a cell-based assay. We discovered that the hydroxymethylketone and ketobenzothiazole warheads were equipotent to the nitrile warhead, suggesting that these analogs can also be used for treating coronavirus infections. 相似文献
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39.
Jianwei Zhang Yu Du Chengping Hu Yan Liu Jinxing Liu Ang Gao Yingxin Zhao Yujie Zhou 《Journal of atherosclerosis and thrombosis》2022,29(4):482
Aims: The associations between increased glycated albumin (GA) in the serum and diabetic complications and mortality have been revealed in the general population. However, less is known regarding the prognostic value of GA in patients diagnosed with acute coronary syndrome (ACS). Methods: In this study, all patients admitted for ACS who underwent a successful percutaneous coronary intervention (PCI) at our center from January 2018 to February 2019 were retrospectively examined. Clinical characteristics, laboratory results (e.g., serum GA levels), and procedural details were collected. The primary outcome included a composite of major adverse cardio-cerebral events (MACCE), such as death, myocardial infarction, stroke, and unplanned revascularization. The association between serum GA levels and clinical outcomes was tested in three multivariable models using Cox proportional hazard analysis. Subgroup analysis was performed in patients who were diagnosed with diabetes versus patients without diabetes. Results: A total of 1,806 ACS patients (mean age of 59.4 years; 77.8% were men; 44.9% were diagnosed with diabetes) were enrolled in this study, where the majority exhibited unstable angina (81.6%) and showed preserved left ventricular systolic function. Patients in the high GA level group were commonly female and were more likely to have metabolic disorders and to exhibit severe CAD (all p <0.05). MACCE occurred in 126 patients (7.0%) during a mean follow-up time of 17.2 months. The cumulative risk of MACCE at the 18-month follow-up visit significantly increased in a stepwise fashion along with increased GA levels (log-rank p =0.018) in the serum. The association between serum GA levels and MACCE was further determined after adjusting traditional risk factors and hemoglobin A1c (HbA1c) (GA, per 1% increase: hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.06–1.13; GA, higher vs. lower tertial: HR 1.92, 95% CI 1.01–3.67). In a subgroup analysis, the prognostic role of serum GA only existed in diabetic patients, even when adjusting for traditional risk factors and HbA1c levels. Conclusions: Elevated GA levels in the serum were associated with poor intermediate-term outcomes in low-risk ACS patients who underwent PCI, especially in patients with preexisting diabetes. 相似文献
40.
目的 探讨内脏动脉瘤的外科治疗方法。方法 回顾性分析2002年2月至2010年6月收治的19例内脏动脉瘤患者外科治疗的临床资料,包括脾动脉瘤7例、肝右动脉瘤1例、胃左动脉瘤1例、胰十二指肠动脉瘤3例、胃十二指肠动脉瘤2例、肠系膜上动脉瘤、结肠中动脉瘤和左结肠动脉瘤各1例、肾动脉瘤2例。其中破裂12例。按照手术方式分为两组,介入栓塞治疗组13例,开放手术组6例。结果 4例栓塞后再出血,2例行手术探查止血、2例行二次栓塞后都得以成功止血。8例动脉瘤破裂伴休克患者术后均停止出血。1例胰十二指肠动脉瘤栓塞后出现十二指肠不全梗阻。2例脾动脉瘤患者术后出现部分脾梗死。术后随访18例,随访2 ~ 103个月,无动脉瘤复发。结论 以支配脏器和动脉解剖的特点作为内脏动脉瘤选择手术方案的主要依据。腔内治疗和开放手术在治疗内脏动脉瘤方面均有效,而对于假性动脉瘤破裂患者,腔内治疗效果满意。 相似文献