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PurposeTo create a nonsurgical animal model of osteoarthritis (OA) to evaluate the effects of embolotherapy during geniculate artery embolization (GAE).Materials and MethodsFluoroscopy-guided injections of 700 mg of sodium monoiodoacetate were performed into the left stifle in 6 rams. Kinematic data were collected before and after induction. At 10 weeks after induction, Subjects 1 and 4–6 underwent magnetic resonance (MR) imaging with dynamic contrast enhancement (DCE) and Subjects 1, 3, and 4–6 underwent angiography with angiographic scoring to identify regions with greatest disease severity for superselective embolization (75–250-μm microspheres). Target vessel size was measured. At 24 weeks after angiography, DCE-MR imaging, angiography, and euthanasia were performed, and bilateral stifles were harvested. Medial/lateral tibial and femoral condylar, patellar, and synovial samples were cut, preserved, decalcified, and scored using the Osteoarthritis Research Society International criteria. The stifle and synovium Whole-Organ Magnetic Resonance Imaging Score and Multicenter Osteoarthritis Study score were determined. The volume transfer constant (Ktrans) and extracellular volume fraction (ve) were calculated from DCE-MR imaging along the lateral synovial regions of interest.ResultsThe mean gross and microscopic pathological scores were elevated at 38 and 61, respectively. Mean synovitis score was elevated at 9.2. Mean pre-embolization and postembolization angiographic scores were 5 and 3.8, respectively. Mean superior, transverse, and inferior geniculate artery diameters were 3.1 mm ± 1.21, 2.0 mm ± 0.50, and 1.6 mm ± 0.41 mm, respectively. Mean pre-embolization and postembolization cartilage and synovitis scores were elevated at 35.13 and 73.3 and 5.5 and 9.2, respectively. The Ktrans/ve values of Subjects 4, 5, and 6 were elevated at 0.049/0.38, 0.074/0.53, and 0.065/0.51, respectively. Altered gait of the hind limb was observed in all subjects after induction, with reduced joint mobility. No skin necrosis or osteonecrosis was observed.ConclusionsA nonsurgical ovine animal knee OA model was created, which allowed the collection of angiographic, histopathological, MR imaging, and kinematic data to study the effects of GAE.  相似文献   
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Cystic fibrosis is characterized by abnormal mucous secretions in the lungs that favor the proliferation of colonizing bacteria, with Pseudomonas aeruginosa and Staphylococcus aureus being the most isolated, however, other less known species could also have an impact on the health of the patient. Here we demonstrate the isolation and antibiotic resistance profiles of Inquilinus limosus, a rarely reported multidrug resistant bacterium, and compare them to a co-infectant strain of Pseudomonas aeruginosa. Likewise, we found that co-infection with both bacteria promotes increased formation of neutrophil extracellular traps, which can have an impact on the disease severity and make treatment difficult.  相似文献   
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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   
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《Saudi Dental Journal》2022,34(7):565-571
PurposeThis study aimed to evaluate the neuroprotective ability of the conditioned medium of stem cells from human exfoliated deciduous teeth (CM-SHED) to prevent glutamate-induced apoptosis of neural progenitors.Materials and methodsNeural progenitors were isolated from two-day-old rat brains, and the conditioned medium was obtained from a mesenchymal stem cell SHED. Four groups were examined: neural progenitor cells cultured in neurobasal medium with (N + ) and without (N-) glutamate and glycine, and neural progenitor cells cultured in CM-SHED with (K + ) and without (K-) glutamate and glycine.ResultsThe expression of GABA A1 receptor (GABAAR1) messenger RNA (mRNA) in neural progenitor measured by real-time quantitative PCR. GABA contents were measured by enzyme-linked immunosorbent assay, whereas the apoptosis markers caspase-3 and 7-aminoactinomycin D were analysed with a Muse® cell analyzer. The viability of neural progenitor cells in the K + group (78.05 %) was higher than the control group N- (73.22 %) and lower in the N + group (68.90 %) than in the control group. The K + group showed the highest GABA content, which significantly differed from that in the other groups, whereas the lowest content was observed in the N + group. The expression level of GABAAR1 mRNA in the K + group was the highest compared to that in the other groups. CM-SHED potently protected the neural progenitors from apoptosis.ConclusionsCM-SHED may effectively prevent glutamate-induced apoptosis of neural progenitors.  相似文献   
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Background and aimsIntermittent fasting reduces risk of interrelated cardiometabolic diseases, including type 2 diabetes and heart failure (HF). Previously, we reported that intermittent fasting reduced homeostasis model assessment of insulin resistance (HOMA-IR) and Metabolic Syndrome Score (MSS) in the WONDERFUL Trial. Galectin-3 may act to reduce insulin resistance. This post hoc evaluation assessed whether intermittent fasting increased galectin-3.Methods and resultsThe WONDERFUL Trial enrolled adults ages 21–70 years with ≥1 metabolic syndrome features or type 2 diabetes who were not taking anti-diabetic medication, were free of statins, and had elevated LDL-C. Subjects were randomized to water-only 24-h intermittent fasting conducted twice-per-week for 4 weeks and once-per-week for 22 weeks or to a parallel control arm with ad libitum energy intake. The study evaluated 26-week change scores of galectin-3 and other biomarkers. Overall, n = 67 subjects (intermittent fasting: n = 36; control: n = 31) completed the trial and had galectin-3 results. At 26-weeks, the galectin-3 change score was increased by intermittent fasting (median: 0.793 ng/mL, IQR: ?0.538, 2.245) versus control (median: ?0.332 ng/mL, IQR: ?0.992, 0.776; p = 0.021). Galectin-3 changes correlated inversely with 26-week change scores of HOMA-IR (r = ?0.288, p = 0.018) and MSS (r = ?0.238, p = 0.052). Other HF biomarkers were unchanged by fasting.ConclusionA 24-h water-only intermittent fasting regimen increased galectin-3. The fasting-triggered galectin-3 elevation was inversely correlated with declines in HOMA-IR and MSS. This may be an evolutionary adaptive survival response that protects human health by modifying disease risks, including by reducing inflammation and insulin resistance.Trial registrationClinicaltrials.gov, NCT02770313 (registered on May 12, 2016; first subject enrolled: November 30, 2016; final subject's 26-week study visit: February 19, 2020).  相似文献   
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The Extracellular Vesicle Flow Cytometry Working Group ( http://www.evflowcytometry.org ) is formed by members of the International Society for Extracellular Vesicles (ISEV), the International Society for Advancement of Cytometry (ISAC), and the International Society on Thrombosis and Haemostasis (ISTH). This working group of flow cytometry experts develops guidelines for best practices regarding flow cytometry detection of extracellular vesicles. To improve rigor and standardization, this working group published a framework outlining the minimal information to report about a flow cytometry experiment on extracellular vesicles (MIFlowCyt-EV) in the Journal of Extracellular Vesicles, the ISEV journal, in 2020. In parallel, an article explaining MIFlowCyt-EV was published in Cytometry Part A, one of the ISAC journals, and now will be introduced to the ISTH as an SSC Communication in the Journal of Thrombosis and Haemostasis. The goal of this SSC Communication is to explain why flow cytometry is becoming the instrument of choice to characterize single extracellular vesicles, the obstacles that have been identified and (mostly) overcome by developing procedures to calibrate flow cytometers, and the relevance of reporting minimal information to improve reliability and reproducibility of experiments in which flow cytometers are used for characterization of extracellular vesicles.  相似文献   
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目的 研究唾液细胞外囊泡miRNA-143/145表达水平与女性绝经后骨质疏松的相关性,以探讨其对雌激素缺乏性骨质疏松的诊断价值。方法 选取在我院进行种植牙手术的绝经前后女性患者,采用CBCT对松质骨进行骨参数分析,测量患者骨密度差异;选择在我院进行住院手术的绝经期前后女性,分别收集血清、唾液样本,提取细胞外囊泡;透射电镜观察血清和唾液中细胞外囊泡形态;ELISA检测血清中雌激素表达水平;qRT-PCR检测血清和唾液细胞外囊泡中miRNA-143/145水平。结果 经分析发现,绝经后女性雌激素水平明显下降,并伴有骨密度的显著降低;经透射电镜观察,血清和唾液中细胞外囊泡为直径约100 nm的杯状双层膜样结构;和绝经前相比,绝经后女性血循环中miRNA-143/145的表达显著升高;进一步检测唾液中miRNA-143/145表达,呈现相似的趋势。结论 基于唾液细胞外囊泡中miRNA-143/145检测结果与血清检测相似,提示唾液检测作为一种无创性操作方式,更便于临床医生为女性绝经后骨质疏松状态做出诊断。  相似文献   
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