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991.
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993.
目的探讨载淫羊藿苷/凹凸棒石/Ⅰ型胶原/聚己内酯(icariin/ attapulgite/collagen type Ⅰ/polycaprolactone,ICA/ATP/ColⅠ/PCL)复合支架修复兔胫骨缺损的效果。方法利用溶液铸浇-粒子滤沥法分别构建 ICA/20%ATP/ColⅠ/PCL(支架 1)、ICA/30%ATP/ColⅠ/PCL(支架 2)、20%ATP/ColⅠ/PCL(支架 3)、30%ATP/ColⅠ/PCL(支架 4)复合支架材料,采用扫描电镜观察支架 2 交联前、后结构特征,测量支架 2、4 的表面接触角检测材料吸水性能,采用体外降解实验评价支架 2 的药物缓释效果。取 30 只雄性日本大耳白兔,体质量(2.0±0.1)kg,随机分为 A、B、C、D、E 5 组,每组 6 只;制备直径 1 cm 双侧胫骨缺损模型后,A 组不植入任何材料,B~E 组分别于骨缺损处植入支架 3、支架 4、支架 1、支架 2。术后 4、8、12 周大体观察骨缺损修复效果;行 HE、Masson 染色以及成骨特异性转录因子 RUNX2、成骨相关转录因子 Osterix(OSX)、ColⅠ、骨桥蛋白(osteopontin,OPN)抗体的免疫组织化学染色,观察不同支架材料修复骨缺损效果。结果扫描电镜观察示,支架 2 为多孔结构,交联前结构疏松,交联后结构致密;表面接触角检测示支架为疏水性材料,且支架 2 疏水性比支架 4 更高;药物体外缓释效果显示支架 2 上药物能微量长效释放。动物体内植入实验中,大体观察示术后 4、12 周 D、E 组缺损明显小于 A、B、C 组。HE 和 Masson 染色示,术后 4 周 A 组缺损区域充满大量结缔组织,B、C 组可见大量纤维组织,D、E 组可见少量新生骨;术后 8 周各组新生骨比 4 周时增加;术后 12 周 A 组缺损区域仍以纤维组织为主,B、C 组可见少量新生骨组织,D、E 组可见大量新生骨组织,尤以 E 组明显,且大部分支架降解。免疫组织化学染色示,术后 4 周,D、E 组新生组织中 RUNX2 和 OSX 表达明显高于其余各组,术后 8、12 周 RUNX2 表达与 4 周相比表达下降;术后 8、12 周与 4 周相比,各组 ColⅠ、OPN 表达均增加,且 D、E 组新生组织中 ColⅠ、OPN 表达明显高于其余各组。结论ICA/ATP/Col Ⅰ/PCL 复合支架具有良好的孔隙率和生物相容性,并具有促成骨作用,可达到良好骨再生和修复效果。 相似文献
994.
995.
Jarogniew J. Łuszczki Paweł Marzeda Agata Gut-Lepiech Maria W. Kondrat-Wróbel Paula Wróblewska-Łuczka Sławomir Karwan Tomasz Plech 《Pharmacological reports : PR》2019,71(2):299-305
Background
To assess the effects of 5-(3-chlorobenzyl)-4-hexyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (TP427) on the protective anticonvulsant action of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) in the tonic-clonic seizure model in mice, an isobolographic transformation of data was used.Methods
Electrically-induced tonic-clonic seizures were experimentally evoked in adult male albino Swiss mice. The anticonvulsant effects of TP427, when used singly, were determined by the calculation of the threshold increasing the dose by 20% (TID20 value). The influence of TP427 on the anticonvulsant potency of four various classical antiepileptic drugs was determined with a subthreshold method. Types of interactions between drugs were determined using the isobolographic transformation of data. Additionally, total brain antiepileptic drug concentrations were measured.Results
TP427, when administered separately, significantly increased the threshold for electroconvulsions. The experimentally determined TID20 value for TP427 was 11.71?mg/kg. Moreover, TP427 (10?mg/kg) significantly increased the anticonvulsant activity of valproate (p?<? 0.01), but not that of carbamazepine, phenobarbital or phenytoin in the mouse tonic-clonic seizure model. Isobolographic transformation of data confirmed that the interaction between TP427 and valproate was synergistic. Pharmacokinetic study revealed that TP427 increased total brain valproate concentrations, and had no impact on total brain concentrations of carbamazepine, phenobarbital or phenytoin in mice.Conclusion
The synergistic interaction between TP427 and valproate in the mouse tonic-clonic seizure model might occur favorable for epilepsy patients in future. The combinations of TP427 with carbamazepine, phenobarbital and phenytoin were additive in the mouse tonic-clonic seizure model and also deserves clinical attention. 相似文献996.
目的探讨复杂人工全膝关节置换术(total knee arthroplasty,TKA)中采用股直肌斜切辅助显露的安全性及有效性。方法回顾分析 2016 年 1 月—2017 年 5 月,采用股直肌斜切辅助显露的 19 例(29 膝)复杂 TKA 患者临床资料。其中男 9 例(13 膝),女 10 例(16 膝);年龄 34~66 岁,平均 50.2 岁。强直性脊柱炎 4 例(8 膝),类风湿性关节炎 5 例(7 膝),膝关节骨关节炎 10 例(14 膝)。病程 8~15 年,平均 10.9 年。Kellgren-LawrenceⅢ级 12 膝,Ⅳ级 17 膝。患者膝关节活动度为(19.86±7.23)°,膝关节学会评分系统(KSS)临床评分(47.86±11.26)分、功能评分(15.52±11.21)分。术后随访纳入并发症、膝关节活动度、KSS 评分、伸膝迟滞发生情况及假体松动情况。结果术后切口均Ⅰ期愈合,无感染及心脑血管意外等并发症发生。患者均获随访,随访时间 25~39 个月,平均 30.3 个月。末次随访时,患者膝关节活动度为(91.03±7.30)°,KSS 临床评分为(83.62±9.99)分、功能评分为(66.38±7.89)分,均较术前明显改善,差异有统计学意义(P<0.05)。3 膝出现伸膝迟滞,分别迟滞 10°、10°、15°。X 线片复查未见假体位置不良、松动及病理性透亮线。 结论复杂 TKA 中采用股直肌斜切能有效显露膝关节术野,减少髌腱撕脱、髌骨骨折以及股四头肌肌腱损伤等并发症的发生;采用 Krackow 肌腱缝合法修复切断的股直肌有利于术后早期膝关节功能锻炼及恢复,而且不会增加并发症发生风险。 相似文献
997.
Necrotizing enterocolitis (NEC), a devastating infant disease characterized by severe intestinal necrosis, its pathogenesis is poorly understood, but appears to be multifactorial and highly associated with immaturity of gastrointestinal tract and immature innate-immune system. Breast-milk is effective strategy to protect infants against NEC. This study is using a NEC rat model to investigate the pathological mechanism of NEC involved intestinal-damages, and the therapeutic mechanism of sialylated human milk oligosaccharides (SHMOs) on NEC rats; also using cell model to investigate the effects of SHMOs on colon-epithelial cells (Caco-2) in-vitro.Extraction and characterization of SHMOs from breast milk, establishment of a NEC rat model, histopathological analysis and mast cell accounting of the terminal ileum were taken; The levels of DPPI, TLR4, IL-6, TNF-α, MMP-2/9 and glutathione were measured using various methods. Caco-2 cells were pre-treated with SHMOs and cultured with LPS, histamine, chymase or DPPI, cell viabilities and mitochondrial membrane potential were examined; flow cytometry was used to detect cell cycle.The accumulation of mast cells was found in the ileum of NEC rats, but prohibited by SHMOs treatment; the increased levels of TLR4, DPPI, IL-6, TNF-α, MMP-2/9 in NEC ileum were suppressed by SHMOs in-vivo. SHMOs prevented Caco-2 cells from LPS, histamine, chymase induced damages by surviving cell viability, regulating G0/G1 and S phase in cell cycles, and increasing mitochondrial membrane potential. These findings provide a new insight into the pharmacological mechanism of SHMOs treatment for NEC and suggest that SHMOs needs well attention for therapeutic aims. 相似文献
998.
目的 观察胃癌组织中抑癌基因PDCD4启动子区甲基化状态及其对PDCD4表达水平的影响并探讨其临床意义。方法 通过免疫组织化学、Western blot法检测胃癌组织中PDCD4蛋白的表达;RT-PCR法检测PDCD4 mRNA的表达;甲基化特异性PCR(MSP)法检测PDCD4启动子区甲基化水平。分析PDCD4表达水平以及启动子甲基化水平与胃癌患者临床病理特征之间的相关性。结果 胃癌组织中PDCD4蛋白及mRNA表达水平均显著降低(P<0.05),甲基化作用显著增强(P<0.05)。PDCD4蛋白表达缺失与胃癌的分化、临床分期以及淋巴结转移密切相关(P<0.05);PDCD4高甲基化与胃癌的淋巴结转移、临床分期密切相关(P<0.05)。PDCD4甲基化水平与PDCD4蛋白以及mRNA表达水平均呈负相关(P<0.05)。结论 胃癌组织中PDCD4表达水平显著降低,并与胃癌发展相关,启动子区高甲基化可能是PDCD4表达缺失的原因。 相似文献
999.
Sanne C. Lith Bram W. van Os Tom T.P. Seijkens Carlie J.M. de Vries 《European journal of immunology》2020,50(11):1643-1652
The nuclear receptor Nur77 is expressed in a multitude of tissues, regulating cell differentiation and homeostasis. Dysregulation of Nur77 signaling is associated with cancer, cardiovascular disease, and disorders of the CNS. The role of Nur77 in T cells has been studied for almost 30 years now. There is a clear appreciation that Nur77 is crucial for apoptosis of self-reactive T cells. However, the regulation and function of Nur77 in mature T cells remains largely unclear. In an exciting development, Nur77 has been recently demonstrated to impinge on cancer immunotherapy involving chimeric antigen receptor (CAR) T cells and tumor infiltrating lymphocytes (TILs). These studies indicated that Nur77 deficiency reduced T cell tolerance and exhaustion, thus raising the effectiveness of immune therapy in mice. Based on these novel insights, it may be proposed that regulation of Nur77 activity holds promise for innovative drug development in the field of cellular immunotherapy in cancer. In this review, we therefore summarize the role of Nur77 in T cell selection and maturation; and further develop the idea of targeting its activity in these cells as a potential strategy to augment current cancer immunotherapy treatments. 相似文献
1000.
《Immunobiology》2020,225(3):151959
AimsNeuromyelitis optica spectrum disorders (NMOSD) are aquaporin-4 antibody-mediated diseases of the central nervous system. Endothelin-1 (ET-1) is an inflammatory cytokine released by vascular endothelial cells and activated astrocytes. Previous studies have reported the aberrant expressions of cytokines/chemokines in patients diagnosed with NMOSD. However, the serum levels of ET-1 in NMOSD patients remain unknown. The purpose of this study was to measure the serum levels of ET-1 and other immune-related cytokines/chemokines in patients with NMOSD, and to investigate the correlation between serum ET-1 levels and clinical characteristics of NMOSD.MethodsThirty-eight patients with NMOSD and twenty-eight healthy controls (HCs) were recruited in this study. The serum concentrations of ET-1 and other cytokines/chemokines were measured, and their correlations to the clinical features of patients with NMOSD were analyzed.ResultsThe serum levels of ET-1 in patients with NMOSD were significantly higher than those in HCs (P = 0.0001). The serum concentrations of ET-1 were positively correlated with the Expanded Disability Status Scale score (r = 0.428, P = 0.0183). High-dose intravenous methylprednisolone treatment significantly reduced the levels of ET-1 and interleukin (IL)-6 in blood, but significantly increased the serum concentrations of IL-10 in NMOSD patients. No correlations were found between serum ET-1 levels and the concentrations of other cytokines/chemokines in these patients.ConclusionET-1 and IL-6 might exert pro-inflammatory effects in the pathogenesis of NMOSD, whereas IL-10 played an anti-inflammatory role in this process. ET-1 might be a potential biomarker for predicting the severity of NMOSD. However, the serum levels of ET-1 were not correlated with the changes of other cytokines/chemokines in patients with NMOSD. The involvement of ET-1 in the development of NMOSD needs to be further studied. 相似文献