首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   15735篇
  免费   1021篇
  国内免费   623篇
耳鼻咽喉   96篇
儿科学   235篇
妇产科学   335篇
基础医学   2925篇
口腔科学   569篇
临床医学   1181篇
内科学   2295篇
皮肤病学   247篇
神经病学   1335篇
特种医学   316篇
外国民族医学   2篇
外科学   1356篇
综合类   1859篇
预防医学   764篇
眼科学   295篇
药学   1879篇
中国医学   184篇
肿瘤学   1506篇
  2023年   99篇
  2022年   173篇
  2021年   289篇
  2020年   271篇
  2019年   248篇
  2018年   279篇
  2017年   321篇
  2016年   365篇
  2015年   447篇
  2014年   723篇
  2013年   1004篇
  2012年   874篇
  2011年   1023篇
  2010年   863篇
  2009年   954篇
  2008年   984篇
  2007年   970篇
  2006年   882篇
  2005年   833篇
  2004年   730篇
  2003年   641篇
  2002年   521篇
  2001年   479篇
  2000年   387篇
  1999年   333篇
  1998年   251篇
  1997年   256篇
  1996年   213篇
  1995年   228篇
  1994年   205篇
  1993年   145篇
  1992年   152篇
  1991年   146篇
  1990年   134篇
  1989年   113篇
  1988年   76篇
  1987年   70篇
  1986年   53篇
  1985年   95篇
  1984年   101篇
  1983年   75篇
  1982年   65篇
  1981年   66篇
  1980年   58篇
  1979年   50篇
  1978年   37篇
  1977年   35篇
  1976年   18篇
  1975年   12篇
  1974年   12篇
排序方式: 共有10000条查询结果,搜索用时 20 毫秒
1.
《Pancreatology》2022,22(7):880-886
BackgroundPremature intracellular trypsinogen activation has long been considered a key initiator of acute pancreatitis (AP). Cathepsin B (CTSB) activates trypsinogen, while cathepsin L (CTSL) inactivates trypsin(ogen), and both proteins play a role in the onset of AP.MethodsAP was induced by 7 hourly intraperitoneal injections of cerulein (50 μg/kg) in wild-type and pancreas-specific conditional Ctsb knockout (CtsbΔpan), Ctsl knockout (CtslΔpan), and Ctsb;Ctsl double-knockout (CtsbΔpan;CtslΔpan) mice. Pancreatic samples were collected and analyzed by histology, immunohistochemistry, real-time PCR, and immunoblots. Trypsin activity was measured in pancreatic homogenates. Peripheral blood was collected, and serum amylase activity was measured.ResultsDouble deletion of Ctsb and Cstl did not affect pancreatic development or mouse growth. After 7 times cerulein injections, double Ctsb and Ctsl deficiency in mouse pancreases increased trypsin activity to the same extent as that in Ctsl-deficient mice, while Ctsb deficiency decreased trypsin activity but did not affect the severity of AP. CtsbΔpan;CtslΔpan mice had comparable serum amylase activity and histopathological changes and displayed similar levels of proinflammatory cytokines, apoptosis, and autophagy activity compared with wild-type, CtsbΔpan, and CtslΔpan mice.ConclusionDouble deletion of Ctsb and Ctsl in the mouse pancreas altered intrapancreatic trypsin activity but did not affect disease severity and inflammatory response after cerulein-induced AP.  相似文献   
2.
多囊卵巢综合征(polycystic ovary syndrome,PCOS)是育龄期女性最常见的内分泌及代谢性疾病之一,PCOS患者发生心血管疾病和2型糖尿病的风险增加。越来越多的研究支持胰岛素抵抗(insulin resistance,IR)是PCOS重要的病理机制之一。血管生成素样蛋白(angiopoietin-like proteins,ANGPTLs)家族是一类与血管生成素结构相似的分泌型糖蛋白,目前已发现8个成员,即ANGPTL1~ANGPTL8。ANGPTLs在PCOS患者血液中表达水平升高,并且与IR程度密切相关,ANGPTLs通过促进脂肪组织炎症、调节胰岛素分泌及磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路等参与了IR和糖代谢,这很可能与PCOS的发病有关。综述ANGPTLs参与IR和糖代谢的机制及其在PCOS中的作用,以期进一步探讨ANGPTLs参与PCOS发病的机制,为预测和治疗PCOS提供新思路。  相似文献   
3.
4.
目的建立一种基于规律成簇的间隔短回文重复序列及其相关蛋白(CRISPR/Cas13a)的乙型肝炎病毒(HBV)共价闭合环状DNA(HBV cccDNA)检测方法。方法提取2017年6月至2020年10月于首都医科大学附属北京佑安医院就诊的4例乙型肝炎患者肝脏总DNA后,使用HindⅢ内切酶和质粒安全性ATP依赖DNA酶(PSAD)分别进行酶切;根据松弛环状DNA(rcDNA)和cccDNA的结构差异,设计特异性扩增HBV cccDNA的引物,对酶切后的产物进行滚环扩增(RCA)和PCR扩增;并筛选crRNA,建立基于CRISPR/Cas13a技术的HBV cccDNA检测新方法。结果利用α-1-抗胰蛋白酶(A1AT)和HBV表面抗原(HBsAg)引物对双重酶切后的产物进行扩增,验证产物中HBV基因组的存在;利用HBV cccDNA和HBV rcDNA引物对PSDA酶切后的产物扩增,验证了产物中只存在HBV cccDNA;利用RCA后的阳性样本作为模板梯度稀释,然后进行PCR扩增转录后使用CRISPR/Cas13a检测,计算出检测下限为10拷贝/μl。结论本研究建立了RCA-PCR-CRISPR-Cas13a的新型检测方法,可对HBV cccDNA进行高灵敏度和高特异性检测,为乙型肝炎患者抗病毒治疗评估、治疗终点的确定以及调整治疗方案提供了有效的监测手段。  相似文献   
5.
目的了解西安儿童医院儿童细菌感染性疾病的病原分布特点和耐药现状,以指导抗菌药物的应用并预防多重耐药菌(MDROs)的产生。方法收集2019年1月至2020年12月西安市儿童医院住院患儿临床分离的菌株,对菌株临床分布特点及耐药性进行分析,并与全国监测数据进行比较。结果共分离出菌株9044株,检出数居前5位依次为凝固酶阴性葡萄球菌(CNS)、大肠埃希菌(Eco)、化脓性链球菌(Spy)、金黄色葡萄球菌(Sau)和嗜麦芽窄食单胞菌(Sma),分别占14.3%(1291/9044)、10.3%(920/9044)、9.6%(870/9044)、9.0%(822/9044)和5.6%(507/9044)。重点耐药菌中耐甲氧西林金黄色葡萄球菌(MRSA)、红霉素耐药肺炎链球菌(ERSP)、碳青霉烯耐药铜绿假单胞菌(CR-Pae)检出率分别为30.1%、92.1%和14.2%,低于全国水平(35.0%、98.8%和23.2%),差异均有统计学意义(χ^(2)=7.89、P=0.01,χ^(2)=75.98、P<0.001,χ^(2)=10.12、P<0.001),而耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)和碳青霉烯耐药鲍曼不动杆菌(CR-Aba)检出率分别为81.8%和68.9%,均高于全国水平(76.4%和54.0%),差异均有统计学意义(χ^(2)=4.78、P=0.03,χ^(2)=11.53、P<0.001)。共检出MDROs 920株,检出率为10.2%(920/9044),最常见的依次为Eco[47.4%(436/920)]、Sau[23.7%(218/920)]和Kpn[13.2%(121/920)];主要分离自脓液[46.1%(424/920)]、呼吸道[28.9%(266/920)]和血液[11.1%(102/920)]。分离细菌对多种抗菌药物呈现不同程度的耐药性,部分菌株耐药率与全国监测数据差异较大,其中Sau和CNS对克林霉素耐药率分别为67.8%(564/832)和65.0%(724/1114),显著高于全国监测数据[30.9%(2645/8561)和25.5%(1409/5524)](χ^(2)=458.8、662.7,P均<0.001);Eco对头孢吡肟、亚胺培南和美罗培南耐药率分别为14.4%(135/935),1.7%(16/935)和1.2%(11/935),显著低于全国水平[22.8%(2181/9567),3.2%(306/9567)和4.2%(402/9567)](χ^(2)=34.62、P<0.001,χ^(2)=6.34、P=0.01,χ^(2)=20.64、P<0.001);Aba对头孢他啶、亚胺培南耐药率分别为65.2%(88/135)和62.5%(84/135),显著高于全国水平[53.4%(1621/3036)和51.9%(1576/3036)](χ^(2)=7.23、P=0.01,χ^(2)=5.51、P=0.02);Pae对哌拉西林、头孢他啶、头孢吡肟、美罗培南耐药率分别为8.6%(20/233),7.7%(18/233),2.7%(6/233)和8.7%(20/233),显著低于监测数据[15.2%(508/3344),14.0%(468/3344),10.2%(341/3344)和20.0%(669/3344)],差异有统计学意义(χ^(2)=7.56、P=0.01,χ^(2)=7.29、P=0.01,χ^(2)=14.45、P<0.001,χ^(2)=18.27、P<0.001)。结论本院儿童感染性疾病常见细菌分布及对多种抗菌药物的耐药率如Sau和CNS对克林霉素,Eco对头孢吡肟、碳青霉烯类抗菌药物,Aba对头孢他啶、亚胺培南以及Pae对β-内酰胺类和碳青霉烯类抗菌药物的耐药性与全国监测水平差异较大,需进一步加强对重点耐药菌如MRCNS、CR-Aba的感染防控,针对本地区细菌感染特点合理应用抗菌药物,对于降低感染率和院内感染播散有重要意义。  相似文献   
6.
《Diagnostic Histopathology》2021,27(12):506-518
Recent discovery of new disease-defining molecular alterations and development of novel targeted therapies has dramatically changed the classification and management of uterine mesenchymal neoplasms. This review discusses diagnostic updates in endometrial stromal sarcoma, PEComa, uterine tumor resembling ovarian sex cord tumor (UTROSCT), inflammatory myofibroblastic tumor, NTRK fusion uterine sarcoma, COL1A1-PDGFB fusion sarcoma, and SMARC-deficient uterine sarcoma. Key clinical, morphologic, immunophenotypic, and molecular features are reviewed, with emphasis on common differential diagnoses and pitfalls, and their impact on prognosis or management. Where applicable, the role of novel targeted therapies is discussed. A stepwise approach to uterine mesenchymal neoplasms can achieve a proper diagnosis and guide appropriate clinical management in most cases. Nonetheless, given the rarity of these tumors, their overlapping pathologic features, and rapid evolution in their classification and management, we advocate a low threshold for diagnostic consultation.  相似文献   
7.
Here, we review the development, morphology, genes, and proteins of claws in reptiles. Claws likely form owing to the inductive influence of phalangeal mesenchyme on the apical epidermis of developing digits, resulting in hyperproliferation and intense protein synthesis in the dorsal epidermis, which forms the unguis. The tip of claws results from prevalent cell proliferation and distal movement along most of the ungueal epidermis in comparison to the ventral surface forming the subunguis. Asymmetrical growth between the unguis and subunguis forces beta-cells from the unguis to rotate into the apical part of the subunguis, sharpening the claw tip. Further sharpening occurs by scratching and mechanical wearing. Ungueal keratinocytes elongate, form an intricate perimeter and cementing junctions, and remain united impeding desquamation. In contrast, thin keratinocytes in the subunguis form a smooth perimeter, accumulate less corneous beta proteins (CBPs) and cysteine-poor intermediate filament (IF)-keratins, and desquamate. In addition to prevalent glycine–cysteine–tyrosine rich CBPs, special cysteine-rich IF-keratins are also synthesized in the claw, generating numerous  S S bonds that harden the thick and compact corneous material. Desquamation and mechanical wear at the tip ensure that the unguis curvature remains approximately stable over time. Reptilian claws are likely very ancient in evolution, although the unguis differentiated like the outer scale surface of scales, while the subunguis might have derived from the inner scale surface. The few hair-like IF-keratins synthesized in reptilian claws indicate that ancestors of sauropsids and mammals shared cysteine-rich IF-keratins. However, the number of these keratins remained low in reptiles, while new types of CBPs function to strengthen claws.  相似文献   
8.
9.
BackgroundIncreasing evidence shows obesity and poor metabolic health are associated with cognitive deficits, but the mechanistic connections have yet to be resolved. We studied rats selectively bred for low and high intrinsic aerobic capacity in order to test the association between low physical fitness, a genetic predisposition for obesity, and brain health. We hypothesized that low-capacity runner (LCR) rats with concurrently greater levels of adiposity would have increased hippocampal inflammation and reduced plasticity compared to the more physically fit high-capacity runner (HCR) rats.MethodsWe examined markers for inflammation and brain plasticity in the hippocampi of LCR rats and compared them to HCR rats. The effect of age was determined by studying the rats at a young age (8 weeks) and later in life (40 weeks). We used western blots and immunohistochemistry to quantify the expression of target proteins.ResultsOur study showed that the number of adult-born new neurons in the hippocampus was significantly lower in LCR rats than it was in HCR rats already at a young age and that the difference became more pronounced with age. The expression of synaptic proteins was higher in young animals relative to older ones. Brain inflammation tended to be higher in LCR rats than it was in the HCR rats, and more prominent in older rats than in young ones.ConclusionOur study is the first to demonstrate that low intrinsic aerobic fitness that is associated with obesity and poor metabolic health is also linked with reduced hippocampal structural plasticity at a young age. Our results also suggest that inflammation of the brain could be one factor mediating the link between obesity and poor cognitive performance.  相似文献   
10.
非小细胞肺癌(Non-small cell lung cancer,NSCLC)占所有肺癌的80%~85%,是全世界发病率和致死率极高的恶性肿瘤。最初NSCLC对现有治疗的反应良好,但最终还是产生了耐药性。因此,有必要探索有效且新颖的治疗方法。随着对NSCLC研究的深入,发现Dickkopf家族蛋白(DKKs)的信号传导在NSCLC发展中扮演重要角色,DKKs是Wnt/β-catenin信号通路的重要调节因子,并与NSCLC细胞增殖、转移和侵袭密切相关。本文主要介绍了DKKs家族成员在NSCLC中的作用机制,讨论了DKKs在NSCLC治疗中的潜力,为进一步防治NSCLC提供了新思路。  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号