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   14917篇
  免费   1212篇
  国内免费   638篇
耳鼻咽喉   131篇
儿科学   142篇
妇产科学   207篇
基础医学   2371篇
口腔科学   1336篇
临床医学   1002篇
内科学   1893篇
皮肤病学   423篇
神经病学   852篇
特种医学   297篇
外国民族医学   4篇
外科学   1879篇
综合类   2251篇
预防医学   446篇
眼科学   477篇
药学   1491篇
  3篇
中国医学   566篇
肿瘤学   996篇
  2024年   2篇
  2023年   169篇
  2022年   198篇
  2021年   393篇
  2020年   466篇
  2019年   385篇
  2018年   423篇
  2017年   446篇
  2016年   451篇
  2015年   597篇
  2014年   921篇
  2013年   1141篇
  2012年   877篇
  2011年   1061篇
  2010年   908篇
  2009年   932篇
  2008年   1018篇
  2007年   962篇
  2006年   913篇
  2005年   773篇
  2004年   708篇
  2003年   620篇
  2002年   438篇
  2001年   348篇
  2000年   232篇
  1999年   225篇
  1998年   184篇
  1997年   130篇
  1996年   129篇
  1995年   119篇
  1994年   99篇
  1993年   96篇
  1992年   67篇
  1991年   60篇
  1990年   54篇
  1989年   37篇
  1988年   33篇
  1987年   26篇
  1986年   14篇
  1985年   30篇
  1984年   30篇
  1983年   7篇
  1982年   9篇
  1981年   7篇
  1980年   10篇
  1979年   4篇
  1978年   5篇
  1977年   3篇
  1976年   2篇
  1974年   2篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
肿瘤致密的细胞外基质(extracellular matrix, ECM)严重限制了纳米药物的深部渗透,削弱了其抗肿瘤效果。基于此,本研究构建了具有肿瘤组织主动深部渗透能力的酵母囊泡仿生纳米药物,以期提高抗肿瘤效果。体外表征结果显示,分离的酵母囊泡(yeast cell vesicles, YCV)为规则球形,分散性良好,粒径约100 nm。以抗肿瘤药物多柔比星(doxorubicin, DOX)为模型药物,构建YCV/DOX纳米药物, DOX的包封率为82.5%,且DOX的释放具有显著的pH依赖性;细胞实验结果显示,相比于脂质体, YCV在3D肿瘤球中表现出更强的渗透能力,推测其机制可能为YCV具有良好的形变能力。4T1荷瘤小鼠(动物实验符合中国实验动物护理和使用准则,并经郑州大学实验动物伦理委员会批准)体内药效实验结果表明, YCV/DOX具有更强的肿瘤组织渗透能力,且有效抑制肿瘤生长。本研究为克服实体瘤的组织屏障和发展新型仿生纳米药物带来新思路。  相似文献   
2.
PurposeTo compare the characteristics of polidocanol (POL) and ethanolamine oleate (EO) sclerosing foams produced by a Shirasu porous glass membrane (SPGM) device with those made using a 3-way stopcock (3WSC).Materials and MethodsFoam half-life times were measured in an ex-vivo benchtop study. Computed tomography (CT) images of each foam were obtained over the time course, and a CT texture analysis was conducted. The bubble size in each foam was measured by an optical microscope.ResultsMedian foam half-life times were longer in the SPGM group than in the 3WSC group (POL: 198 vs 166 s, P = .02; EO: 640 vs 391 s, P < .01). In the CT texture analysis, median standard deviation (SD) and entropy (randomness) were lower, and median energy (uniformity) and gray-level cooccurrence matrix (GLCM) homogeneity were higher in the SPGM group than in the 3WSC group (POL SD: at 30 s and 50–300 s; POL entropy: at 0–60 s; EO SD: at 0–600 s; EO entropy: at 0–460 s; POL energy: at 0–40 s; POL GLCM homogeneity: at 0–250 s; EO energy: at 0–360 s; EO GLCM homogeneity: at 0–480 s; all P < .05). Median bubble diameters in the SPGM group and in the 3WSC group were 69 and 83 μm (P < .01), respectively, in the POL foam; and 36 and 36 μm (P = .45), respectively, in the EO foam.ConclusionsPOL and EO foams had greater uniformity and longer foam half-life time when prepared with an SPGM device than with a 3WSC.  相似文献   
3.
BackgroundGlioma accounts for most central nervous system tumors, and the degree of invasion and malignancy are higher in the recurrent glioma. Photodynamic therapy (PDT) is an effective strategy in glioma. This study aimed to explore the risk factors for re-recurrence after a second glioma surgery and the effects of PDT on re-recurrence.MethodsThis was a retrospective study in the Second Affiliated Hospital of Harbin Medical University in China, and 43 patients that received the secondary surgery for recurrent glioma were included. The Kaplan-Meier test and Cox proportional hazard method were used to analyze.ResultsThe total re-recurrence rate after the second surgery for recurrent glioma was 48.84%. When the age increased by 1, the risk of re-recurrence increased 1.065 times (95% CI 1.000–1.134, P = 0.049). High matrix metalloproteinase (MMP) 2 expression was associated with a significantly higher risk of re-recurrence than low MMP2 expression (HR = 25.550, 95% CI 3.190–204.650, P = 0.002). Pathological grades IV and III were associated with a significantly higher risk of re-recurrence than pathological grade II (HR = 17.121, 95% CI 2.345–124.986, P = 0.005; HR = 2863.470, 95% CI 100.697–81,427.197, P < 0.001). PDT decreased the risk of re-recurrence (HR = 25.550, 95% CI 3.190–204.650, P = 0.002) and increased survival time (HR = 3.611, 95% CI 1.012–12.888, P = 0.048).ConclusionThe age, MMP2 expression, and pathological grade are independent risk factors for re-recurrence after a second surgery for recurrent glioma. PDT during the second surgery decreased the risk of re-recurrence and increased survival time.  相似文献   
4.
Spinster 2 (Spns2) is a transporter that pumps sphingosine-1-phosphate (S1P), a bioactive lipid mediator synthesized in the cytoplasm, out of cells into the inter cellular space. S1P is a signal that modulates cellular behavior during embryonic development, inflammation and tissue repair, etc. A Spns2-null (KO) mouse is born with failure of eyelid closure (eyelid-open-at birth; EOB) and develop corneal fibrosis in adulthood. It remains elusive whether corneal lesion is caused by exposure to keratitis (lagophthalmos) of EOB phenotype or the loss of Spns2 directly perturbs the corneal tissue morphogenesis and intra-eyelid structures. Therefore, we investigated differences between the cornea and ocular adnexa morphogenesis in KO and wild-type (WT) embryos and adults as well.The loss of Spns2 perturbs cornea morphogenesis during embryonic development as early as E16.5 besides EOB phenotype. Histology showed that the corneal stroma was thinner with less extracellular matrix accumulation, e.g., collagen and keratocan in the KO mouse. Epithelial stratification, expression of keratin 12 and formation of desmosomes and hemidesmosomes were also perturbed in these KO corneas. Lacking Spns2 impaired morphogenesis of the Meibomian glands and of orbicularis oculi muscles. KO glands were labeled for ELOVL4 and PPARγ and were Oil-Red O-positive, suggesting KO acinar cells possessed functionality as the glands.This is the first report on the roles of Spns2 in corneal and Meibomian gland morphogenesis. Corneal tissue destruction in an adult KO mouse might be due to not only lagophthalmos but also to an impaired morphogenesis of cornea, Meibomian glands, and orbicularis oculi muscle.  相似文献   
5.
6.
目的探讨兔脱细胞软骨基质颗粒(ACM)的生物相容性,阐明其对SD大鼠脂肪干细胞(ADSCs)软骨内成骨的促进作用。  相似文献   
7.
目的分析复合细胞毒性T淋巴细胞相关蛋白4(CTLA4)的脱钙骨基质(DBM)对T淋巴细胞免疫能力和骨髓间充质干细胞(BMMSCs)迁移能力的体外调控作用。方法通过特殊负压灌注装置将纤维蛋白凝胶复合CTLA4溶液灌注到DBM,构建复合CTLA4的DBM,并通过扫描电镜观察其微观形态。分离外周血单核细胞(PBMCs),通过植物血凝素(PHA)激活T淋巴细胞来构建免疫激活微环境。将复合CTLA4的DBM在培养基中孵育5、10、20、30、40 d,ELISA检测CTLA4的浓度,由此计算CTLA4的累积释放率。将PHA预处理的PBMCs与复合CTLA4的DBM进行Transwell共培养,ELISA检测培养基中IL-2和IFN-γ的含量。分离BMMSCs,Transwell共培养法分析复合CTLA4的DBM对BMMSCs增殖和迁移能力的影响。结果复合CTLA4的DBM结构完整有序,具有良好的三维网络结构。复合材料中CTLA4在5、10、20、30、40 d的累积释放率分别为(11.3%±1.9%)、(27.9%±3.7%)、(48.4%±3.6%)、(62.8%±3.8%)和(83.0%±2.5%)。与单纯的DBM相比,与复合CTLA4的DBM共培养可显著减少培养基中IL-2(P=0.0004)和IFN-γ(P=0.0007)的含量,增强BMMSCs的增殖能力(P=0.0006)和迁移能力(P=0.0004)。结论复合CTLA4的DBM在体外环境下具有抑制T淋巴细胞免疫能力和增强BMMSCs迁移能力的作用。  相似文献   
8.
《Drug discovery today》2022,27(1):223-233
Approaches based on animal and two-dimensional (2D) cell culture models cannot ensure reliable results in modeling novel pathogens or in drug testing in the short term; therefore, there is rising interest in platforms such as organoids. To develop a toolbox that can be used successfully to overcome current issues in modeling various infections, it is essential to provide a framework of recent achievements in applying organoids. Organoids have been used to study viruses, bacteria, and protists that cause, for example, respiratory, gastrointestinal, and liver diseases. Their future as models of infection will be associated with improvements in system complexity, including abilities to model tissue structure, a dynamic microenvironment, and coinfection.Teaser.Organoids are a flexible tool for modelling viral, bacterial and protist infections. They can provide fast and reliable information on the biology of pathogens and in drug screening, and thus have become essential in combatting emerging infectious diseases.  相似文献   
9.
目的:探究理筋手法联合消瘀膏辅助治疗膝骨关节炎的临床疗效。方法:选取2019年7月至2021年2月间在黑龙江中医药大学附属二院推拿科治疗的膝骨关节炎患者70例作为研究对象,按照数字表法分为观察组和对照组,每组35例,对照组患者实施临床常规西医治疗,观察组患者在西医治疗基础上增加中医理筋手法联合消瘀膏治疗。对比分析2组患者临床疗效、膝关节功能和炎症水平、软骨代谢水平情况。结果:观察组疗效显著优于对照组(P<005)。治疗前,2组西安大略和麦克马斯特大学骨关节炎指数量表(WOMAC)各维度评分、血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1)水平比较差异均无统计学意义(P>005),治疗后,2组患者WOMAC各项评分、TNF-α、IL-1水平均下降,且观察组显著低于对照组(P<005)。治疗前,2组患者血清软骨寡聚基质蛋白(COMP)、Ⅱ型胶原羧基端端肽(CTX-Ⅱ)、硫酸角质素(KS)水平比较差异均无统计学意义(P>005),治疗后,2组患者COMP、CTX-Ⅱ、KS水平均下降,且观察组显著低于对照组(P<005)。结论:理筋手法联合消瘀膏治疗能显著提升膝骨关节炎患者临床疗效,改善膝关节功能,下调炎症反应,改善软骨代谢异常。  相似文献   
10.
李晓云  沈正祥  杨丹 《中国骨伤》2022,35(7):655-660
目的:探讨膝骨关节炎(knee osteoarthritis,KOA)患者关节滑液中骨桥蛋白(osteopontin,OPN)和软骨寡聚基质蛋白(cartilage oligomeric matrix protein,COMP)水平与疾病严重程度的相关性。方法:选取2018年2月至2020年5月收治的59例KOA患者作为KOA组,其中男25例,女34例;年龄60~75(65.57±1.56)岁;体质量指数(body mass index,BMI)21.4~30.7(26.12±1.54) kg/m2。采用Kellgren-Lawrence(K-L)分级对X线结果进行评估,其中Ⅱ级(K-L2组)14例,Ⅲ级(K-L3组)27例,Ⅳ级(K-L4组)18例。另选取18例因韧带或半月板疾病进行关节镜检查且无软骨损伤患者作为对照组,男7例,女11例;年龄61~78(64.88±1.60)岁;BMI 22.8~29.9(25.89±1.49) kg/m2。治疗前采集研究对象关节滑液样本,采用酶联免疫吸附试验检测关节滑液OPN、COMP水平,比较KOA组与对照组关节滑液OPN、COMP水平。比较不同K-L分级KOA患者性别、年龄、BMI等临床资料,采用酶联免疫试验检测其关节滑液中白细胞介素-1β(interleukin -1β,IL-1β),OPN,COMP,基质金属蛋白酶3(matrix metalloproteinase -3,MMP-3)水平,比较不同K-L分级KOA患者临床资料和生化指标,采用Logistic回归分析影响KOA患者K-L分级的因素,采用ROC曲线下面积(area under the curve,AUC)预测KOA疾病严重程度。结果:59例KOA患者获得随访,时间8~27(15.75±3.27)个月。KOA组关节滑液OPN、COMP水平高于对照组(P<0.001)。K-L2组、K-L3组、K-L4组IL-1β、OPN、COMP、MMP-3水平比较差异有统计学意义(P<0.001);与K-L2组比较,K-L3、K-L4关节滑液关节滑液IL-1β、OPN、COMP、MMP-3 水平均升高(P<0.05);与K-L3组比较,K-L4关节滑IL-1β、OPN、COMP、MMP-3水平均升高(P<0.05)。多因素Logistic回归分析结果显示:关节滑液OPN、COMP、MMP-3水平是影响KOA患者K-L分级的独立危险因素(OR=6.653, 4.229,1.579,P<0.001)。关节滑液OPN预测K-L4级KOA的AUC为0.720[95%CI(0.588-0.851)],灵敏度为94.4%,特异度为65.9%;关节滑液COMP预测K-L4级KOA的AUC为0.731[95%CI(0.592-0.870)],灵敏度为88.9%,特异度为63.4%;关节滑液OPN联合COMP预测K-L4级KOA的AUC为0.839[95%CI(0.724-0.953)],灵敏度为94.4%,特异度为51.2%;OPN联合COMP预测K-L4级KOA的AUC大于单独OPN、COMP的AUC(Z=4.037,3.540,P<0.05)。结论:KOA患者关节滑液OPN、COMP水平升高,并随着K-L分级增加而升高。关节滑液OPN、COMP是影响KOA患者K-L分级的独立危险因素,二者预测K-L4级KOA 的AUC、灵敏度、特异度高,可用于评估KOA疾病进展。  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