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1.
目的探讨通过下食管括约肌(lower esophageal sphincter,LES)扩张建立咽喉反流性疾病(laryngophyngeal reflux disease,LPRD)模型的可行性。方法18只新西兰白兔随机分为实验组10只和对照组8只,对实验组动物进行LES测压定位后,使用球囊对LES进行注水扩张,对照组同法置入球囊,但不进行球囊注水。扩张前1周及扩张后2周行咽喉及食管下段pH监测,LES平均静息压检测;扩张前1周、扩张后2周及8周行喉镜检查,进行喉镜下反流体征评分;扩张后8周处死动物,对其喉部及食管下段黏膜取材,光镜下观察其病理变化。结果扩张后pH监测验证实验组造模成功8只(80.0%,8/10),实验组扩张前咽喉酸反流时间百分比(%)、反流事件数(次)、反流最长时间(s)分别为0(0,0)、0(0,0)、0(0,0),扩张后分别为17.5(8.2,29.4)、3(1,5.5)、17.2(10.2,30.8),较扩张前增加,差异有统计学意义(P<0.01)。实验组扩张前食管下段pH监测酸反流时间百分比、反流事件数、反流最长时间分别为0(0,0.7)、0(0,1)、0(0,1.2),扩张后分别为23.1(4.8,49.5)、3(1,6)、25.9(11.5,56.8),较扩张前增加,差异有统计学意义(P<0.01)。实验组扩张前LES压力28.0±5.6 mmHg,较扩张后(17.2±3.3 mmHg)升高,差异有统计学差异(P=0.001);实验组扩张前RFS评分3.1±1.2分,扩张后2周为3.6±1.4分,扩张后8周为8.6±2.5分,扩张前和扩张后2周差异无统计学意义(P=0.482),但扩张前与扩张后8周差异有统计学意义(P=0.005)。病理检查示实验组喉部及食管黏膜均可观察到不同程度慢性炎症。结论食管下括约肌球囊扩张可安全、有效地建立LPRD动物模型。  相似文献   
2.
Galactosyl transferase knock-out pig lungs fail rapidly in baboons. Based on previously identified lung xenograft injury mechanisms, additional expression of human complement and coagulation pathway regulatory proteins, anti-inflammatory enzymes and self-recognition receptors, and knock-down of the β4Gal xenoantigen were tested in various combinations. Transient life-supporting GalTKO.hCD46 lung function was consistently observed in association with either hEPCR (n = 15), hTBM (n = 4), or hEPCR.hTFPI (n = 11), but the loss of vascular barrier function in the xenograft and systemic inflammation in the recipient typically occurred within 24 h. Co-expression of hEPCR and hTBM (n = 11) and additionally blocking multiple pro-inflammatory innate and adaptive immune mechanisms was more consistently associated with survival >1 day, with one recipient surviving for 31 days. Combining targeted genetic modifications to the lung xenograft with selective innate and adaptive immune suppression enables prolonged initial life-supporting lung function and extends lung xenograft recipient survival, and illustrates residual barriers and candidate treatment strategies that may enable the clinical application of other organ xenografts.  相似文献   
3.
邓蕊  柴克霞  马苗 《西部医学》2022,34(8):1102-1108
目的 探讨NADPH氧化酶中的NOX2和NOX4介导的活性氧(ROS)在特发性炎性肌病(IIM)发病机制中的作用及意义。方法将14只健康雌性BALB/c小鼠随机分为对照组(n=6)和EAM组(n=8),EAM组小鼠采用豚鼠骨骼肌匀浆蛋白免疫诱导实验性自身免疫性肌炎动物模型。观察小鼠的体重变化、临床表现,测定其血清肌酶水平、四肢肌力及骨骼肌组织病理改变;并采用免疫组织化学法、分光光度法和ELISA法分别检测各组小鼠骨骼肌组织中NOX2、NOX4、NADPH及ROS的表达情况或含量。结果 与对照组相比,末次免疫后1周EAM组小鼠体重下降,差异有统计学意义(P<0.05)。HE染色结果显示,对照组小鼠骨骼肌纤维大小、形态、结构基本正常,有少量炎性细胞浸润,未见肌纤维萎缩、变性、坏死;EAM组小鼠骨骼肌纤维大小不一、粗细不等,有大量炎性细胞浸润,可见不同程度的萎缩、变性、坏死;EAM组小鼠骨骼肌组织HE染色病理学评分显著高于对照组(P<0.05)。与对照组相比,EAM组小鼠骨骼肌组织中NADPH含量降低、ROS含量升高(P<0.05)。免疫组化染色结果显示,NOX2和NOX4在EAM组小鼠骨骼肌组织中的表达均高于对照组(P<0.05)。Pearson相关分析结果显示,EAM组小鼠骨骼肌组织中ROS的含量与NOX2、NOX4的免疫组化评分均呈正相关(P<0.05),而与NADPH的含量呈负相关(P<0.05);EAM组小鼠骨骼肌组织HE染色病理学评分与NOX2、NOX4的免疫组化评分及ROS的含量均呈正相关(P<0.05),而与NADPH的含量呈负相关(P<0.05)。结论 NADPH氧化酶中的NOX2和NOX4可能通过消耗NADPH产生大量的ROS,导致组织细胞氧化性损伤并诱导铁死亡反应来参与IIM的发病;NADPH、NOX2、NOX4和ROS有望成为新的评价IIM肌肉组织损伤程度的指标。  相似文献   
4.
《Diagnostic Histopathology》2022,28(11):493-500
After decades of relative stagnation lung cancer is emerging as a disease type where rapid progress is being made in diagnosis and therapy, as well as in our understanding of disease biology. Much of this progress is of immediate impact to diagnosticians, and more is likely to affect diagnostic practice in the near future. In this review we seek to briefly summarize several key areas of active research of immediate or probable imminent value to trainee and consultant pulmonary pathologists alike. We cover some major changes in tumour classification, grading, and patient stratification, as well as considering the state of the art in machine-assisted interpretation of lung cancer histology, and the use of genetically modified lung cancer models.  相似文献   
5.
背景:股骨头坏死发病机制仍需要进一步研究,因此需要建立一个能够高度模拟人类股骨头坏死的动物模型,而如何正确评价股骨头坏死动物模型,是建立股骨头坏死动物模型的前提条件。目的:归纳总结近几年国内外对股骨头坏死动物模型的评价方法,综述各评价方法的优缺点,并探索新的评价方法,为动物模型的建立提供参考。方法:以“股骨头坏死,动物模型,评价方法”为检索词检索CNKI中国知网、万方、维普数据库,以“osteonecrosis of femoral head,femoral head necrosis,animal model,evaluation methods”为检索词检索PubMed、Web of Science及Medline数据库,检索2010年1月至2020年9月发表关于股骨头坏死动物模型评价方法的文献。结果与结论:①根据纳入标准通过阅读文献进行初步筛选,共获得51篇文章进行综述,其中中文文献33篇,英文文献18篇;②近年来,随着影像技术的发展和新技术的引入,股骨头坏死动物模型评估方法的选择增多,而选择合理的评价方式能减少建立动物模型过程中的工作量,并为后续研究提供参考,因此需要继续完善和改进。  相似文献   
6.
Infection of bone tissue, or osteomyelitis, has become a growing concern in modern healthcare due in no small part to a rise in antibiotic resistance among bacteria, notably Staphylococcus aureus. The current standard of care involves aggressive, prolonged antibiotic therapy combined with surgical debridement of infected tissues. While this treatment may be sufficient for resolving a portion of cases, recurrences of the infection and associated risks including toxicity with long‐term antibiotic usage have been reported. Therefore, there exists a need to produce safer, more efficacious options of treatment for osteomyelitis. In order to test treatment regimens, animal models that closely mimic the clinical condition and allow for accurate evaluation of therapeutics are necessary. Establishing a model that replicates features of osteomyelitis in humans continues to be a challenge to scientists, as there are many variables involved, including choosing an appropriate species and method to establish infection. This review addresses the refinement of animal models of osteomyelitis to reflect the clinical disease and test prospective therapeutics. The aim of this review is to explore studies regarding the use of animals for osteomyelitis therapeutics research and encourage further development of such animal models for the translation of results from the animal experiment to human medicine.  相似文献   
7.
基于血栓闭塞性脉管炎的临床病症特点,通过查阅相关文献,整理分析并建立血栓闭塞性脉管炎的西医诊断标准与中医辨证标准,总结血栓闭塞性脉管炎动物模型的造模方法、造模对象、模型优缺点。分析其与中西医临床病症特点的吻合度,总结发现血栓闭塞性脉管炎动物模型与西医临床病症吻合度较高,与中医寒湿阻络证和热毒伤阴证吻合度较高,与湿热毒盛证和气血两虚证吻合度较低,没有与血脉淤阻证相吻合的动物模型。患肢病变程度、病理、血液流变学指标(血液黏度、红细胞沉降率)为最常检测指标。现阶段相对于大量临床治疗血栓闭塞性脉管炎的病例报道,实验研究相对薄弱,建立合理的模型判断量化标准,复制与中医证候吻合度更高的动物模型是日后的研究重点。  相似文献   
8.
Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra‐ and extracellular modifications are needed to make functional collagen molecules, intracellular post‐translational modifications of proline and lysine residues having key roles in this. In this article, we provide a review on the enzymes responsible for the proline and lysine modifications, that is collagen prolyl 4‐hydroxylases, 3‐hydroxylases and lysyl hydroxylases, and discuss their biological functions and involvement in diseases.  相似文献   
9.
目的分析2005~2019年湖北省肾综合征出血热(HFRS)疫情流行特征,为制定预防控制措施提供科学依据。方法收集2005~2019年湖北省HFRS的疫情资料和鼠监测资料,开展描述性分析和相关分析。结果湖北省2005~2019年HFRS年平均发病率为0.56/10万,发病高峰为每年5~7月、11月至次年1月,2016年以后病例数上升明显,病例以男性、农民为主,35~69岁人群占79.93%,其中60岁及以上的占27.75%(1354/4879)。2019年湖北省HFRS发病率居前五位的地市为潜江市(6.21/10万)、天门市(4.01/10万)、荆州市(3.01/10万)、仙桃市(2.28/10万)和荆门市(2.04/10万)。发病率和鼠密度呈正相关(r_s=0.57,P<0.05)。结论近年来湖北省HFRS疫情有所回升,应重点关注潜江市、天门市和荆州市等江汉平原地区和60岁及以上人群,开展"监测、健教、灭鼠、免疫"并重的综合性防控措施。  相似文献   
10.
Obstructive sleep apnea (OSA) occurs exclusively during sleep due to reduced tongue motor activity. Withdrawal of excitatory inputs to the hypoglossal motor nucleus (HMN) from wake to sleep contributes to this reduced activity. Several awake–active neurotransmitters with inputs to the HMN (e.g. serotonin [5-HT]) inhibit K+ leak mediated by TASK-1/3 channels on hypoglossal motoneurons, leading to increased neuronal activity in vitro. We hypothesize that TASK channel inhibition at the HMN will increase tongue muscle activity in vivo and modulate responses to 5-HT. We first microperfused the HMN of anesthetized rats with TASK channel inhibitors: doxapram (75 μM, n = 9), A1899 (25 μM, n = 9), ML365 (25 μM, n = 9), acidified artificial cerebrospinal fluid (ACSF, pH = 6.25, n = 9); and a TASK channel activator terbinafine (50 μM, n = 9); all with and without co-applied 5-HT (10 mM). 5-HT alone at the HMN increased tongue motor activity (202.8% ± 45.9%, p < 0.001). However, neither the TASK channel inhibitors, nor activator, at the HMN changed baseline tongue activity (p > 0.716) or responses to 5-HT (p > 0.127). Tonic tongue motor responses to 5-HT at the HMN were also not different (p > 0.05) between ChAT-Cre:TASKf/f mice (n = 8) lacking TASK-1/3 channels on cholinergic neurons versus controls (n = 10). In freely behaving rats (n = 9), microperfusion of A1899 into the HMN increased within-breath phasic tongue motor activity in wakefulness only (p = 0.005) but not sleep, with no effects on tonic activity across all sleep–wake states. Together, the findings suggest robust maintenance of tongue motor activity despite various strategies for TASK channel manipulation targeting the HMN in vivo, and thus currently do not support this target and direction for potential OSA pharmacotherapy.  相似文献   
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