全文获取类型
收费全文 | 41772篇 |
免费 | 4855篇 |
国内免费 | 3159篇 |
学科分类
医药卫生 | 49786篇 |
出版年
2024年 | 74篇 |
2023年 | 692篇 |
2022年 | 1360篇 |
2021年 | 2204篇 |
2020年 | 1965篇 |
2019年 | 1489篇 |
2018年 | 1481篇 |
2017年 | 1435篇 |
2016年 | 1274篇 |
2015年 | 2013篇 |
2014年 | 2602篇 |
2013年 | 2488篇 |
2012年 | 3316篇 |
2011年 | 3734篇 |
2010年 | 2792篇 |
2009年 | 2338篇 |
2008年 | 2626篇 |
2007年 | 2490篇 |
2006年 | 2225篇 |
2005年 | 1944篇 |
2004年 | 1511篇 |
2003年 | 1459篇 |
2002年 | 1238篇 |
2001年 | 1002篇 |
2000年 | 799篇 |
1999年 | 671篇 |
1998年 | 383篇 |
1997年 | 460篇 |
1996年 | 302篇 |
1995年 | 287篇 |
1994年 | 231篇 |
1993年 | 168篇 |
1992年 | 141篇 |
1991年 | 119篇 |
1990年 | 100篇 |
1989年 | 97篇 |
1988年 | 75篇 |
1987年 | 65篇 |
1986年 | 40篇 |
1985年 | 36篇 |
1984年 | 13篇 |
1983年 | 8篇 |
1982年 | 12篇 |
1981年 | 9篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1973年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
Qunchuan Zhuang Aling Shen Liya Liu Meizhu Wu Zhiqing Shen Huixin Liu Ying Cheng Xiaoying Lin Xiangyan Wu Wei Lin Jiapeng Li Yuying Han Xiaoping Chen Qi Chen Jun Peng 《Oncology Letters》2021,22(1)
Valuable diagnostic and prognostic biomarkers are urgently needed for colorectal cancer (CRC), which is one of the leading causes of mortality worldwide. Previous studies have reported altered expression of a mucin-like protein Fc fragment of IgG binding protein (FCGBP) in various types of cancer, but its potential diagnostic, prognostic and immunological roles in CRC remain to be determined. Therefore, the aim of current study was to investigate the potential roles of FCGBP in CRC. The present study investigated FCGBP mutations and changes in its expression levels using a combination of microarray and public dataset analyses, as well as immunohistochemistry. The results demonstrated a 10.5% mutation frequency in the FCGBP coding sequence in CRC tissues, and identified decreased FCGBP mRNA or protein expression levels in colorectal adenoma and CRC (compared with those in normal colorectal tissues from healthy control subjects), including pathologically advanced CRC (stage III+IV vs. I+II). Survival analysis using the GEPIA and Kaplan-Meier Plotter databases revealed that low FCGBP expression levels were associated with short overall, disease-free, relapse-free and event-free survival times in patients with CRC. Notably, analysis using the online Tumor IMmune Estimation Resource database revealed a positive correlation between FCGBP expression levels and the extent of infiltrating immune cells, such as B cells and dendritic cells. Consistently, the expression levels of most markers (51/57) for various types of immune cells were significantly correlated with FCGBP expression levels in CRC tissues. These findings suggested that FCGBP may serve as a diagnostic and prognostic biomarker, and that FCGBP may be associated with immune infiltration in CRC. 相似文献
52.
Qiang Fu Le Xu Yiwei Wang Qi Jiang Zheng Liu Junyu Zhang Quan Zhou Han Zeng Shanyou Tong Tao Wang Yangyang Qi Baoying Hu Hangcheng Fu Huyang Xie Lin Zhou Yuan Chang Yu Zhu Bo Dai Jiejie Xu 《European urology》2019,75(5):752-763
Background
Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities.Objective
To seek a potential therapeutic target in glutamine-addicted ccRCC.Design, setting, and participants
Tumors from ccRCC patients from a Shanghai cohort and ccRCC tumor data from The Cancer Genome Atlas (TCGA) cohort were analyzed. In vivo and in vitro studies were conducted with fresh human ccRCC tumors and murine tumor cells.Outcome measurements and statistical analysis
Immune cell numbers and functions were analyzed by flow cytometry. Glutamine and cytokine concentrations were determined. Survival was compared between different subpopulations of patients using Kaplan-Meier and Cox regression analyses.Results and limitations
We found that in ccRCC, high interleukin (IL)-23 expression was significantly associated with poor survival in both TCGA (overall survival [OS] hazard ratio [HR] = 2.04, cancer-specific survival [CSS] HR = 2.95; all p < 0.001) and Shanghai (OS HR = 2.07, CSS HR = 3.92; all p < 0.001) cohorts. IL-23 blockade prolongs the survival of tumor-bearing mice, promotes T-cell cytotoxicity in in vitro cultures of human ccRCC tumors, and augments the therapeutic benefits of anti-PD-1 antibodies. Mechanistically, glutamine consumption by ccRCC tumor cells results in the local deprivation of extracellular glutamine, which induces IL-23 secretion by tumor-infiltrating macrophages via the activation of hypoxia-inducible factor 1α (HIF1α). IL-23 activates regulatory T-cell proliferation and promotes IL-10 and transforming growth factor β expression, thereby suppressing tumor cell killing by cytotoxic lymphocytes. The positive correlations between glutamine metabolism, IL-23 levels, and Treg responses are confirmed in both TCGA cohort and tumors from Shanghai ccRCC patients. Study limitations include the unclear impacts of glutamine deprivation and IL-23 on other immune cells.Conclusions
Macrophage-secreted IL-23 enhanced Treg functions in glutamine-addicted tumors; thus, IL-23 is a promising target for immunotherapy in ccRCC.Patient summary
In this study, we analyzed the immune components in glutamine-addicted clear cell renal cell carcinoma (ccRCC) tumors from two patient cohorts and conducted both in vitro and in vivo studies. We found that ccRCC tumor cell-intrinsic glutamine metabolism orchestrates immune evasion via interleukin (IL)-23, and IL-23–high patients had significantly poorer survival than IL-23–low patients. IL-23 should thus be considered a therapeutic target in ccRCC, either alone or in combination with immune checkpoint inhibitors. 相似文献53.
Xin Yuan Xin Huang Ben Wang Yin‐xue Huang Yi‐ya Zhang Yan Tang Jin‐yan Yang Qi Chen Dan Jian Hong‐fu Xie Wei Shi Ji Li 《The Journal of dermatology》2019,46(3):219-225
Although patients with rosacea often consult dermatologists for dietary factors that might be related to their skin disorders, few studies have been conducted to research the relationship between rosacea and dietary factors. The purpose of this study was to evaluate the potential relationship between rosacea and diet among the large Chinese population with rosacea, which would provide dietary guidelines for patients with rosacea. A multicenter case–control study was conducted. The feeding frequency 2 years before the occurrence of rosacea was collected by standardized questionnaires. Multiple logistic regression analysis was used to calculate risks related to the diet. One thousand three hundred and forty‐seven patients with rosacea and 1290 controls were enrolled in our study. We found that high‐frequency intake of fatty food and tea presented a positive correlation with rosacea, while high‐frequency dairy product intake showed significant negative correlation with rosacea. Sweet food, coffee and spicy food appeared to be independent of any subset of rosacea in our study. However, high‐frequency dairy product intake showed a borderline beneficial effect on rosacea severity. We further analyzed the correlation between diet and the subtype of rosacea. We found that high‐frequency fatty intake was associated with erythematotelangiectatic rosacea (ETR) and phymatous rosacea, while high‐frequency tea intake was only associated with ETR. In addition, high‐frequency dairy product intake showed negative correlations with ETR and papulopustular rosacea. Rosacea is associated with some dietary factors, and our study is valuable in establishing dietary guidelines to prevent and improve rosacea. 相似文献
54.
55.
56.
摘 要 目的:探讨黄芪汤加减治疗慢性阻塞性肺疾病急性加重期(AECOPD)的临床疗效。方法:采用随机数字表法将166例AECOPD患者随机分为常规组和观察组各83例。常规组采用常规西医方法治疗,观察组在常规组的基础上给予黄芪汤加减治疗。观察两组治疗前后第1秒用力呼气量(FEV1)、用力肺活量(FVC)、FEV1占FVC的百分比(FEV1/FVC%)、动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、肿瘤坏死因子 α(TNF α)、白细胞介素 1β(IL 1β)、白细胞介素 6(IL 6)水平。结果:两组治疗后FEV1、FEV1/FVC、PaO2水平与治疗前相比较均显著升高(P<0.05),且观察组与同期常规组相比较均显著升高(P<0.05);两组治疗后PaCO2、TNF α、IL 1β、IL 6水平与治疗前相比较均显著降低(P<0.05),且观察组与同期常规组相比较均显著降低(P<0.05)。结论:黄芪汤加减治疗AECOPD可降低患者炎症反应水平,改善动脉血气和肺功能,提高治疗效果,值得临床应用。 相似文献
57.
58.
Haofan Yin Jinye Xie Ping Jiang Xi Jiang Deyu Duan Junhua Qi Zhaofan Luo Caiqi Ma Honghai Hong 《American journal of cancer research》2020,10(11):3666
Colorectal cancer (CRC) is one of the top three most deadly cancers despite using chemotherapy based on oxaliplatin or irinotecan combined with targeted therapy. Chiauranib has recently been identified to be a promising anticancer candidate with impressive efficacy and safety. However, the role and molecular mechanisms of Chiauranib in the treatment of CRC remain to be elucidated. Our study shows that Chiauranib inhibits cell proliferation and induces apoptosis in KRAS wild-type CRC cells in a dose- and time-dependent manner, but not mutation ones. Meanwhile, Chiauranib increases ROS production in KRAS wild-type CRC cells. Moreover, Chiauranib selectively suppresses KRAS wild-type CRC cells growth in vivo. Mechanistically, Chiauranib inhibits KRAS wild-type CRC cells by triggering ROS production via activating the p53 signaling pathway. Further, KRAS mutation CRC cells are resistant to Chiauranib by increasing Nrf2 to stably elevate the basal antioxidant program and thereby lower intracellular ROS induced by Chiauranib. Our findings provide the rationale for further clinical evaluation of Chiauranib as a therapeutic agent in treating KRAS wild-type CRC. 相似文献
60.
目的 了解老年住院患者跌倒伤害事件的发生特征,探索各特征之间的关联性,旨在为制定跌倒伤害预防措施提供参考。方法 回顾性分析上海市3所综合性医疗机构2014年1月至2018年12月发生的115例老年住院患者跌倒伤害事件,采用Aprior算法对跌倒伤害事件发生特征进行关联规则的数据挖掘。结果 通过设定筛选条件共得到473条强关联规则,结合护理专业知识最终得到9条具有临床实际意义的强关联规则,主要包括发生时间为00:01~06:59、3~6种并存疾病和未主动寻求帮助等。结论 老年住院患者跌倒伤害事件的发生有一定的特征,挖掘出的关联规则能够为护理人员提供跌倒伤害高频场景的指导意见,以此识别易导致跌伤的高危人群及环境,为预防跌倒伤害项目提供较好的案例支持。 相似文献