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1.
Microtubule-severing proteins (MTSPs), are a family of proteins which use adenosine triphosphate to sever microtubules. MTSPs have been shown to play an important role in multiple microtubule-involved cellular processes. One member of this family, fidgetin (FIGN), is also involved in male fertility; however, no studies have explored its roles in female fertility. In this study, we found mouse fidgetin is rich within oocyte zona pellucida (ZP) and is the only MTSP member to do so. Fidgetin also appears to interact with all three ZP proteins. These findings prompted us to propose that fidgetin might prevent polyspermy. Results from in vitro maturation oocytes analysis showed that fidgetin knockdown did cause polyspermy. We then deleted all three fidgetin isoforms with CRISPR/Cas9 technologies; however, female mice remained healthy and with normal fertility. Of all mouse MTSPs, only the mRNA level of fidgetin-like 1 (FIGNL1) significantly increased. Therefore, we assert that fidgetin-like 1 compensates fidgetin's roles in fidgetin knockout female mice.  相似文献   
2.
It has been reported that the histone/protein deacetylase SIRT1-AMP-activated protein kinase (SIRT1-AMPK) signaling pathway may play a role in the effects of dihydromyricetin (DHM) on improving triglyceride (TG) accumulation and insulin resistance in liver cells. Therefore, we aimed to further observe the effect of DHM on liver fat deposition in high-fat diet (HFD)-induced obese mice and explore its possible mechanism. C57BL/6J mice were fed with a normal diet (ND) and HFD and were treated with or without low-dose (125 mg/kg) or high-dose (250 mg/kg) DHM for 16 weeks, respectively. During the experiment, body weight was checked every 2 weeks. After 16 weeks, the orbital vein was bled, the animals were sacrificed, and the subscapular, epididymal, and inguinal fat were collected and weighed with an electronic scale. An automatic biochemical analyzer was used to determine the levels of serum triglyceride (TG), serum total cholesterol (TC), serum high-density lipoprotein (HDL), and serum low-density lipoprotein (LDL). The livers were stained with hematoxylin-eosin staining (H&E) and Oil Red O to detect liver fat deposition. A colorimetric method was used to detect liver MDA and SOD contents. Quantitative real-time PCR (qRT-PCR) was used to detect the gene expressions of related indicators, such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), acetyl-CoA carboxyl acetyl-CoA carboxylase (ACC), sterol regulatory element-binding protein-1c (SREBP-1), fatty acid synthetase (FAS), peroxisome proliferator activation receptor alpha (peroxisome proliferator-activated receptor-alpha, PPARα), palmitoyltransferase 1 (carnitine palmitoyltransferase 1, CPT1), SIRT1, and AMPK. Western blotting analysis was used to detect the protein expression levels of SIRT1, AMPK, SIRT1-AMPK, ACC, SREBP-1, FAS, PPARα, and CPT1. Results showed that compared with the ND group, the weight and body fat of the mice in the HFD group were increased significantly. The levels of TG, TC, and LDL were increased, the level of HDL was decreased, the volume of hepatocytes was increased, the number of lipid droplets, fat deposition, MDA, IL-6, IL-8, TNF-α, SREBP-1c, FAS, ACC1, SIRT1, and AMPK protein levels were significantly increased, and the SOD activity, PPARα, CPT1, SIRT1 mRNA, AMPK mRNA, PPARα, CPT1 levels were significantly decreased. DHM could significantly reverse the changes of the above indexes in HFD mice, while DHM had no significant effect on the above indexes in ND mice. Collectively, our findings revealed that DHM improved liver fat deposition in HFD-induced obese mice, and the mechanism might be related to inhibition of oxidative stress, inflammation, lipid synthesis, and promotion of lipid decomposition.  相似文献   
3.
目的探讨补肾活血方通过信号转导与转录激活子3(STAT3)通路抑制骨细胞的凋亡对骨质疏松的治疗作用。方法选取SPF级健康雌性C57BL/6小鼠75只,随机分为正常对照组11只及造模组64只。造模组采用去势法建立骨质疏松症模型,正常对照组仅暴露双侧卵巢而不切除。将造模成功的小鼠随机分为模型组、补肾活血方低、中、高剂量组及阳性对照组,各12只。模型组和正常对照组分别灌胃给予蒸馏水5 mL·kg-1,1次/d;补肾活血方低、中、高剂量组分别灌胃给予1.79、3.57、7.14 g·mL-1补肾活血方药液5 mL·kg-1,1次/d;阳性对照组灌胃给予0.14 mg·mL-1尼尔雌醇混悬液5 mL·kg-1,1次/d。各组小鼠均治疗12周。检测比较各组骨形态参数,骨细胞凋亡指数(AI),以及骨组织B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、Janus激酶2(JAK2)、STAT3表达水平。结果与模型组比较,各组小鼠骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)及骨密度(BMD)值较高,骨组织Bcl-2蛋白表达水平较高,且补肾活血方低剂量组<补肾活血方中剂量组<补肾活血方高剂量组和阳性对照组,差异有统计学意义(P<0.05)。与模型组比较,各组小鼠骨组织AI较低,骨组织Bax蛋白表达水平较低,骨组织JAK2、STAT3表达水平较低,且补肾活血方低剂量组>补肾活血方中剂量组>补肾活血方高剂量组和阳性对照组,差异有统计学意义(P<0.05)。结论补肾活血方能剂量依赖性的增加骨质疏松小鼠骨密度,增加骨小梁厚度和数量,抑制骨细胞凋亡,其作用可能与抑制STAT3信号通路,调节凋亡相关蛋白Bcl-2、Bax表达有关。  相似文献   
4.
目的:探讨甘草干姜汤(LDGD)对荷乳腺癌小鼠肿瘤生长、免疫器官及肝肾功能的影响。方法:雌性BALB/c小鼠随机分为5组:正常对照组,模型对照组,LDGD低、中、高剂量组(分别为0.1、0.3、0.9g/kg)。正常对照组小鼠灌胃给予蒸馏水,其他各组小鼠接种乳腺癌4T1细胞后,次日开始LDGD低、中、高剂量组小鼠连续灌胃给药20d,模型对照组小鼠给予相应体积的蒸馏水。测定各组小鼠的体质量、胸腺系数、脾脏系数、肝脏系数、肾脏系数、血清肝功能、肾功能生化指标及肿瘤体积、质量,HE染色后观察荷瘤小鼠的肿瘤组织病理变化。结果:与模型对照组相比,LDGD高剂量组小鼠肿瘤生长受到明显抑制,抑瘤率为(44.76±0.06)%(P<0.01),中剂量组抑瘤率为(15.68±0.21)%(P<0.05),低剂量组无明显抑瘤作用;肿瘤组织病理切片HE染色结果表明,LDGD高剂量组中肿瘤坏死灶区域显著增多;各剂量组LDGD对小鼠体质量均无明显影响,不同剂量LDGD组的胸腺系数、肝脏系数、肾脏系数均无明显变化,脾脏系数下降;LDGD高剂量组ALP和CRE与正常对照组小鼠的差异有统计学意义(P<0.05),但与模型对照组相比无明显差异,其他肝肾血生化指标与正常对照组小鼠比较差异均无统计学意义。结论:高剂量LDGD对4T1荷瘤小鼠的肿瘤生长具有明显的抑制作用,无明显免疫抑制作用和肝肾毒性。  相似文献   
5.
目的 研究麻杏纤畅酥对便秘小鼠润肠通便与肠道短链脂肪酸的作用。方法 采用复方地芬诺酯构建小鼠便秘模型,将小鼠随机分为5组:正常组、便秘模型组、阳性对照组、麻杏纤畅酥高剂量实验组和低剂量实验组,检测小鼠排便情况、肠道蠕动及粪便中短链脂肪酸含量等指标。结果 与对照组比较,便秘模型组小鼠的首粒黑便时间明显延长(P<0.05),4 h内粪便粒数、质量、含水量和小肠墨汁推进率均明显降低(P<0.05),说明成功构建小鼠便秘模型。与便秘模型组比较,麻杏纤畅酥可以有效减少小鼠首粒黑便时间(P<0.05),并且能增加粪便粒数(P<0.05)、质量(P<0.05)和粪便含水量(P<0.05),促进便秘小鼠小肠墨汁推进 (P<0.05),提高结肠肌层厚度(P<0.05),促进小鼠肠道代谢产生异丁酸、丁酸、异戊酸和戊酸。结论 麻杏纤畅酥有效促进便秘小鼠肠道蠕动并缓解了便秘,具有润肠通便的作用,本研究为麻杏纤畅酥的保健功效提供了依据。  相似文献   
6.
目的 探讨矢车菊素-3-O-葡萄糖苷(C3G)对小鼠蛛网膜下腔出血(SAH)后早期脑损伤(EBI)的影响及作用机制。方法 取72只雄性C57小鼠随机分成6组:假手术组、SAH组、溶剂组、低剂量C3G组(10 mg/kg)、中剂量C3G组((20 mg/kg)、高剂量C3G组(30 mg/kg);每组12只。应用颈动脉穿刺法制作小鼠SAH模型,术后24 h进行Garcia评分和平衡木评分评估神经功能;每组小鼠随机取6只取外周血检测活性氧(ROS)和丙二醛(MDA)含量,然后取出完整脑组织进行SAH出血评分、脑水含量检测;每组剩余6只小鼠取外周血检测GSH/GSSG水平,然后取脑组织应用免疫印迹法检测PKA、p-PKA、CREB、p-CREB和GCLC表达水平。结果 与假手术组相比,SAH组小鼠神经功能评分明显下降(P<0.05),脑水含量、SAH出血评分、外周血ROS和MDA含量均显著增加(P<0.05),外周血GSH/GSSG比值明显下降(P<0.05),脑组织p-PKA、p-CREB和GCLC表达明显上调(P<0.05)。C3G明显增加小鼠神经功评分(P<0.05),明显降低SAH评分降低、脑含水量(P<0.05),明显降低外周血ROS、MDA含量(P<0.05),明显增加外周血GSH/GSSG比值(P<0.05),明显下调脑组织p-PKA、p-CREB和GCLC表达(P<0.05)。结论 C3G明显改善小鼠SAH后EBI,其机制可能是抑制PKA/CREB信号通路,下调GCLC表达,进而抑制氧化应激损伤。  相似文献   
7.
ObjectivesOriginal odontoblasts and regenerated odontoblast-like cells (OBLCs) may differently regulate Nestin expression. This study aimed to investigate the role of the subodontoblastic layer (SOBL) using green fluorescent protein (GFP) reactivity in the process of OBLC differentiation after tooth drilling in Nestin-enhanced GFP transgenic mice.MethodsA groove-shaped cavity was prepared on the mesial surface of the maxillary first molars of 5- or 6-week-old mice under deep anesthesia. Immunohistochemical staining for Nestin and GFP and Nestin in situ hybridization were conducted on the sections obtained at 1–14 days postoperative.ResultsOdontoblasts showed intense endogenous Nestin protein and mRNA expression, whereas the coronal SOBL cells showed a Nestin-GFP–positive reaction in the control groups. The injured odontoblasts had significantly decreased Nestin immunoreactivity as well as decreased expression of Nestin mRNA 1–2 days after the injury; subsequently, newly differentiated OBLCs were arranged along the pulp–dentin border, with significantly increased Nestin expression as well as increased expression of Nestin mRNA on days 3–5 to form reparative dentin. Nestin-GFP–positive cells at the pulp–dentin border significantly increased in number on days 1 and 2. GFP(+)/Nestin(+) and GFP(?)/Nestin(+) cells were intermingled in the newly differentiated OBLCs.ConclusionsThe commitment of Nestin-GFP–positive cells into Nestin-positive OBLCs suggests that the restriction of endogenous Nestin protein and mRNA expression in the static SOBL cells was removed by exogenous stimuli, resulting in their migration along the pulp–dentin border and their differentiation into OBLCs.  相似文献   
8.
《Vaccine》2022,40(6):934-944
Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.  相似文献   
9.
背景 狼疮肾炎(LN)是系统性红斑狼疮严重并发症之一,相关研究表明中药复方肾怡(SY)可以调节机体免疫及抑制肾脏纤维化。目前运用复方SY治疗LN的疗效及机制尚不清楚。 目的 探究复方SY对LN小鼠的治疗作用及补体旁路途径激活的影响。 方法 2021年4—7月,选取35只SPF级MRL/lpr小鼠(8周龄)、6只SPF级C57BL/6J小鼠(8周龄)进行实验。将MRL/lpr小鼠依据随机数字表法分为MRL/lpr组(n=8)及SY低剂量组(n=9)、SY中剂量组(n=9)、SY高剂量组(n=9),C57BL/6J小鼠为正常对照组(n=6)。SY低、中、高剂量组分别以15.34、46.02、92.04 g/kg剂量进行复方SY汤剂灌胃,正常对照组及MRL/lpr组以0.5 ml 0.9%氯化钠溶液灌胃。从小鼠12周龄开始干预,1次/d,持续14周。观察各组动物体征,检测尿蛋白与肌酐比值(UPCR),血清抗双链DNA抗体(anti-dsDNA)、抗核抗体(ANA)水平,肾脏组织病理情况,肾脏组织C3、免疫球蛋白G(IgG)、C5b-9免疫沉积情况,肾脏组织α平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(CollagenⅠ)、Fibronectin及补体蛋白水平。 结果 截至干预结束,正常对照组6只小鼠存活,MRL/lpr组3只小鼠存活,SY低、中、高剂量组分别有5、7、9只小鼠存活。(1)正常对照组、SY中剂量组、SY高剂量组小鼠体征量化分值均低于MRL/lpr组(P<0.05)。(2)正常对照组、SY各剂量组小鼠干预第9、10、11、12、13周UPCR均低于MRL/lpr组(P<0.05)。(3)正常对照组、SY低剂量组、SY高剂量组小鼠干预14周后血清anti-dsDNA水平低于MRL/lpr组(P<0.05);正常对照组、SY各剂量组小鼠干预14周后血清ANA水平低于MRL/lpr组(P<0.05)。(4)干预14周后,HE染色可见MRL/lpr组小鼠肾小球内有免疫复合物沉积,PAS染色可见肾小球内有新月体形成;HE染色可见SY各剂量组小鼠肾小球大致正常,而PAS染色可见SY中、高剂量组小鼠肾小球内有系膜细胞增生,伴少量炎细胞浸润。(5)正常对照组、SY各剂量组小鼠干预14周后肾脏组织C3、C5b-9沉积低于MRL/lpr组(P<0.05);SY低剂量组、SY高剂量组小鼠干预14周后肾脏组织IgG免疫沉积低于MRL/lpr组(P<0.05)。(6)SY高剂量组小鼠干预14周后肾脏组织CollagenⅠ、Fibronectin 、C3、C5、CD35蛋白水平低于MRL/lpr组(P<0.05);SY低、中剂量组小鼠干预14周后肾脏组织Fibronectin、C3、C5、CD35蛋白水平低于MRL/lpr组(P<0.05);正常对照组小鼠干预14周后肾脏组织Fibronectin蛋白水平低于MRL/lpr组(P<0.05)。 结论 复方SY可改善MRL/lpr小鼠狼疮肾脏损伤,延缓疾病进展,其作用机制可能是通过抑制补体旁路途径的激活。  相似文献   
10.
目的 研究二甲双胍处理对淀粉样蛋白前体蛋白/早老素基因1(APP/PS1)转基因小鼠神经保护作用及机制。方法 将APP/PS1转基因小鼠分成模型组和实验组,将同窝野生型小鼠作为正常组,每组16只。实验组给予二甲双胍350 mg·kg-1·d-1,正常组和模型组给予标准饮用水,连续4个月。用水迷宫实验检测3组小鼠逃生时间,以蛋白质印迹法检测沉默信息调节因子2同源蛋白1(SIRT1)、β淀粉蛋白前体蛋白(APP)、APPβ位点剪切酶1(BACE1)、β羧基末端片段(β-CTF)和核转录因子kappa B(NF-κB),酶联免疫吸附实验检测β-淀粉样蛋白(Aβ40)和β-淀粉样蛋白42(Aβ42),脑切片荧光染色检测老年斑数量,高尔基染色检测树突棘密度。结果 正常组、模型组和实验组于水迷宫实验第6天的逃生时间分别为(30.08±4.26),(54.71±6.58)和(34.56±3.27)s;这3组间树突棘密度分别为(1.68±0.17),(1.05±0.17)和(1.60±0.21)cell·μm-1。模型组和实验组的BAC...  相似文献   
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