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51.
Jun Zhu Liang Wang Yifan Zhou Jun Hao Shuai Wang Lei Liu Jipeng Li 《Journal of gastrointestinal oncology.》2020,11(6):1381
BackgroundThe innovation of immune checkpoint blockade (ICB) represents a promising shift in the treatment of advanced hepatocellular carcinoma (HCC). However, response to ICB has varied largely due to the high tumor heterogeneity and complex tumor microenvironment (TME). The competitive endogenous RNA (ceRNA) network also plays an important role in tumor occurrence and progression, but its relation with tumor-infiltrating immune cells (TICs) remains largely unexplored in HCC. The overriding objective of our study was thus to construct a prognosis-related risk model and to further evaluate the relationship between ceRNA networks and TICs.MethodsDifferentially expressed gene (DEG) analysis was performed to identify the differentially expressed RNAs. Lasso and multivariable Cox regression analyses were used to construct risk models, which were assessed by the area under the receiver operating characteristic curve (AUC of ROC) and Kaplan-Meier (K-M) curves. Then, a single-sample gene set enrichment analysis (ssGSEA) algorithm was adopted to dissect the TICs in HCC samples. Nomograms were constructed and calibration curves were used to verify the discrimination and accuracy of the nomograms. Finally, integration analysis was performed to validate the correlation of ceRNA and TICs.ResultsIn the study, 7 differentially expressed RNAs [5 messenger RNA s (mRNAs) and 2 micro RNAs (miRNAs)] were incorporated to construct a ceRNA risk model. The AUC of the 1-, 3-, and 5-year overall survival (OS) were 0.784, 0.685, and 0.691 respectively. Likewise, 7 types TICs were in the TICs signature model and the AUC of the 1-, 3-, and 5-year OS were 0.706, 0.731, and 0.721 respectively. The integration analysis showed that 7 pairs of mRNA-TICs and 1 pair of miRNA-TICs had a close relation (all correlation coefficients >0.2, P<0.001).ConclusionsThrough constructing two risk models based on ceRNA network and TICs, we identified the hub RNAs and key TICs in the progression and prognosis of HCC, and further explored the relationship between ceRNA and TME. Importantly, targeting these hub RNAs may facilitate the remodeling of the TME and be a potential therapeutic alternative to enhancing the response to ICB, thus improving the prognosis of HCC patients. 相似文献
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53.
Luyao Chen Yongpeng Xie Xin Ma Yu Zhang Xintao Li Fan Zhang Yu Gao Yang Fan Liangyou Gu Lei Wang Xu Zhang Bin Fu 《Molecular carcinogenesis》2020,59(10):1159-1173
Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss-of-function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/β-catenin signaling as well as its target genes, c-Myc and cyclin D1. Interesting, the tumor-suppressive function of SOX6 was proved to be dependent on its specific high-mobility-group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/β-catenin signaling pathway in an HMG domain-dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC. 相似文献
54.
Juan Tong HuiLan Liu ChangCheng Zheng XiaoYu Zhu BaoLin Tang Xiang Wan Wen Yao KaiDi Song Lei Zhang XuHan Zhang ZiMin Sun 《Pediatric transplantation》2020,24(2)
This is a retrospective study to evaluate the efficacy and safety of umbilical cord blood–derived mesenchymal stromal cells (MSCs) for the treatment of pediatric patients with severe BK virus–associated late‐onset hemorrhagic cystitis (BKV‐HC) after unrelated cord blood transplantation (UCBT). Thirteen pediatric patients with severe BKV‐HC from December 2013 to December 2015 were treated with MSCs. The number of MSCs transfused in each session was 1 × 106/kg once a week until the symptoms improved. The median follow‐up time was 1432 (89‐2080) days. The median frequency of MSC infusion was 2 (1‐3), with eight cured cases and five effective cases; the total efficacy rate was 100%. The copy number of urine BKV DNA was 4.43 (0.36‐56.9) ×108/mL before MSC infusion and 2.67 (0‐56.3) ×108/mL after MSC infusion; the difference was not significant (P = .219). There were no significant differences in the overall survival, disease‐free survival, and the incidence of relapse and acute and chronic graft‐versus‐host disease between the MSC infusion group and non‐MSC infusion group. There was also no significant difference in the cytomegalovirus, Epstein‐Barr virus (EBV), and fungal and bacterial infection rates between the two groups. Although umbilical cord blood–derived MSCs do not reduce the number of BKV DNA copies in the urine, the cells have a high efficacy rate and minimal side effects in treating severe BKV‐HC after UCBT among pediatric patients. MSCs do not affect the rates of relapse, long‐term infection, or survival of patients with leukemia. 相似文献
55.
目的:探讨维生素D受体基因多态性与特发性癫痫的相关性。方法:通过病例对照研究方法,选取91例特发性癫痫患者作为病例组,另选取同期105例健康者作为对照组,抽取所有研究对象外周静脉血提取DNA,采用PCR直接测序法进行维生素D受体基因BsmI(rs1544410)、FokI(rs2228570)、Cdx2(rs11568820)位点多态性检测。结果:病例组与对照组的BsmI与FokI位点基因型频率和等位基因频率无显著差异(P>0.05);Cdx2位点基因型频率存在显著差异(χ2=6.67,P=0.036),等位基因频率无显著差异,该位点发生A/G变异,分布不处于Hardy-Weinberg遗传平衡。在Cdx2位点基因型与特发性癫痫关联性分析中,病例组中Cdx2位点AG基因型是特发性癫痫发病的危险因素(OR=2.222,95% CI:1.190~4.150,P=0.027)。结论:维生素D受体基因Cdx2位点多态性与特发性癫痫具有关联性。 相似文献
56.
The authors argue that in preventing and controlling the pandemic of Covid-19, we should have taken an offensive or proactive strategy rather than a defensive or reactionary one because the former type of approach can bring about more health benefits and fewer harms than can the latter. The offensive or proactive approach consists of two parts: The first part is to preemptively establish a barrier between a novel virus and humans in order to prevent the spillover of the virus into humans, and the second part is that, when a spillover fails to be prevented, we should take public interventions, such as contact tracing, social distancing, and quarantine and isolation, as early as when there are several dozens or one hundred or more cases that manifest symptoms with an unknown etiology in order to prevent an epidemic that is still limited to relatively small groups from developing into an outbreak. 相似文献
57.
基于对北京市居民对基本社会医疗保险制度的调查及《北京市统计年鉴》的数据,运用卫生资源分布图、集中指数和卡瓦尼指数等方法从资源总体配置公平性、卫生筹资公平性、卫生资源分布公平性3个方面分析北京市2017年、2018年卫生资源配置的情况。2017年、2018年的集中指数、基尼系数、卡瓦尼指数分别为-0.148、0.244、-0.392及-0.065、0.220、-0.285。并针对性提出统筹城乡基本医保,重视卫生资源的合理配置,保障低收入人群诊疗权益,满足不同人群对医保的需求,增加制度的灵活性,使医保向更公平的方向发展等可操作性政策建议。 相似文献
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59.
目的以新冠肺炎致病菌2019-nCoV,中东呼吸综合征相关冠状病毒MERS-CoV和严重急性呼吸综合征相关冠状病毒SARS-CoV为代表的冠状病毒成为最近重大公共卫生关注焦点。研发更好的防控措施需要更好地认识冠状病毒,尤其是其基因组和复制分子生物学。方法文献综述和基因组序列分析。结果全球14673篇相关文章,美国NCBI有40个冠状病毒全基因组序列,GEO(Gene expression omnibus)有33个冠状病毒相关转录组数据。结论冠状病毒基因组具有独特的性质,复制特点,不少病毒蛋白具有多功能,包括与宿主相互作用,影响宿主蛋白质翻译后修饰如泛素化和去泛素化,调控宿主免疫病理。这些为疫苗、诊断和药物等新防控措施研发提供了基础。 相似文献
60.