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951.
Dealmy Delgadillo Olivier Barbier Gerardo Sierra Jose L. Reyes 《Fundamental & clinical pharmacology》2014,28(2):170-179
End‐stage renal disease is a cause for death worldwide. Renal transplant is a therapeutic alternative, restricted by the scant number of donors. Function of the donor kidney is under risk of adverse circumstances such as fibrosis, where profibrotic effect of transforming growth factor beta 1 (TGF‐β1) plays a key role. Efforts to diminish risks of damage in the remnant kidney of the donor are required. Vitamin A represents one alternative. It has beneficial effects on some nephropathies, mainly those related to oxidative stress. It also participates in normal intrauterine renal development. We studied the effect of all‐trans retinoic acid (ATRA), active form of vitamin A, on postnephrectomy compensatory growth, in male or female rats. Compensatory growth and renal function were evaluated on four experimental groups: Control without treatment (CTL), ATRA‐treated intact rats (CTL + RA), nephrectomized rats (NFX), and ATRA‐treated nephrectomized rats (NFX + RA). We evaluated glomerular function (inulin clearance), tubular function (fractional excretions of sodium and potassium), and urinary flow. Renal mass was also estimated. In ATRA‐treated animals, compensatory growth was higher than in nephrectomized rats without treatment. Hyperfiltration after nephrectomy was less intense in ATRA‐treated female than in male rats. In tubular functions, effect of ATRA was more evident in female than in male rats. Glomerular expression of TGF‐β1 was lower in ATRA‐treated animals than in controls. ATRA reduced intensity and duration of compensatory changes after nephrectomy, improving recovery. 相似文献
952.
Neil B. Marya Patrick D. Powers Larissa Fujii-Lau Barham K. Abu Dayyeh Ferga C. Gleeson Shigao Chen Zaiyang Long David M. Hough Vinay Chandrasekhara Prasad G. Iyer Elizabeth Rajan William Sanchez Tarek Sawas Andrew C. Storm Kenneth K. Wang Michael J. Levy 《Gastrointestinal endoscopy》2021,93(5):1121-1130.e1
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953.
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954.
Vanessa Moñivas Palomero Alejandro Durante-Lopez Mario Torres Sanabria Javier Segovia Cubero Jesús González-Mirelis Jorge Vazquez Lopez-Ibor Sara M. Navarro Rico Isabel Krsnik Fernando Dominguez Alejandro Martinez Mingo Francisco J. Hernandez-Perez Gibanel Cavero Susana Mingo Santos 《Journal of the American Society of Echocardiography》2019,32(7):845-853.e1
955.
目的:探讨前列腺素E联合连续肾替代治疗(CRRT)对脓毒症合并急性肾损伤(AKI)患者预后的影响。方法:选取89例脓毒症合并AKI患者为研究对象,采用随机数字表法分为对照组(n=44)和观察组(n=45),分别采取CRRT及前列腺素E联合CRRT治疗。比较2组患者预后转归情况,检测并比较2组患者治疗前后血清炎性因子、肾功能及免疫功能指标。结果:观察组ICU治疗时间及住院时间较对照组明显缩短(P<0.05);对照组死亡14例(31.82%),观察组死亡9例(20.00%),2组患者死亡率无明显差异(P>0.05)。与治疗前比较,治疗后2组血清TNF-α、IL-6、hs-CRP含量降低,BUN、SCr含量升高(P<0.05),且观察组上述指标均低于对照组(P<0.05)。与治疗前比较,治疗后2组CD4+/CD8+及观察组NK细胞比例及IgG、IgA、IgM含量均明显升高(P<0.05),且观察组高于对照组(P<0.05)。与治疗前比较,治疗后2组Marshall评分、APACHEⅡ评分下降(P<0.05),且观察组低于对照组(P<0.05)。结论:前列腺素E联合CRRT治疗脓毒症合并AKI可显著降低患者炎性因子水平,改善患者肾功能和免疫功能,效果优于单独CRRT治疗。 相似文献
956.
目的:研究服用硫唑嘌呤(AZA)中国肾移植患者红细胞(RBC)内活性代谢物6-硫鸟嘌呤核苷酸(6-TGNs)分布特征及影响因素,为临床合理应用嘌呤类药物提供依据。方法:以89例中国肾移植患者为研究对象,关联分析年龄、性别、体质量、AZA剂量和TPMT活性对RBC内6-TGNs浓度的影响,并应用SPSS v20.0软件进行多元线性回归分析。结果:89例中国肾移植患者RBC内6-TGNs浓度呈非正态分布(P<0.000 1),6-TGNs浓度中位数为167.60(四分位间距,108.10~300.80) pmol/8×108 RBC,个体间差异约24.3倍。关联分析显示患者年龄、性别、体质量、TPMT活性对6-TGNs浓度均无显著影响(P>0.05);而AZA剂量与6-TGNs浓度间呈显著正相关性(rs=0.307 1,P<0.01)。多元线性回归分析显示,RBC内6-TGNs浓度与AZA剂量间呈显著正相关(P<0.001),与TPMT活性呈显著负相关(P<0.05)。结论:AZA剂量和RBC内TPMT活性协同影响嘌呤类药物活性代谢物6-TGNs浓度,进而影响该类药物临床疗效和毒性反应。 相似文献
957.
958.
959.
《Best Practice & Research: Clinical Haematology》2020,33(1):101146
Over the past years, the emergence of liquid biopsy technologies has dramatically expanded our ability to assess multiple myeloma without the need for invasive sampling. Interrogation of cell-free DNA from the peripheral blood recapitulates the mutational landscape at excellent concordance with matching bone marrow aspirates. It can quantify disease burden and identify previously undetected resistance mechanisms which may inform clinical management in real-time. The convenience of sample acquisition and storage provides strong procedural benefits over currently available testing. Further investigations will have to define the role of cell-free DNA as a diagnostic measure by determining clinically relevant tumor thresholds in comparison to existing routine parameters. This review presents an overview of currently available assays and discusses the clinical value, potential and limitations of cell-free DNA technologies for the assessment of this challenging disease. 相似文献
960.