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1.
目的 探讨慢性乙型肝炎(CHB)患者肝X受体α(LXRα)和细胞色素P450亚型7A1(CYP7A1)基因表达水平与肝组织病理学炎症和纤维化程度的关系。方法 2019年1月~2020年10月我院收治的CHB患者118例,均接受肝穿刺活检,将炎症活动度分级>G2和肝纤维化分期>S2定义为肝组织炎症或纤维化程度显著;采用免疫组织化学染色法检测肝组织LXRα和CYP7A1表达,采用RT-PCR法检测LXRα mRNA和CYP7A1 mRNA水平。结果 118例CHB患者肝组织LXRα和CYP7A1蛋白和/或其mRNA阳性分别为78.0%和73.7%;38例肝组织显著炎症组LXRα mRNA和其蛋白(AOD)水平分别为(0.6±0.2)和(0.3±0.1),显著高于80例非显著炎症患者[分别为(0.4±0.1)和(0.1±0.0),P<0.05],CYP7A1 mRNA和其蛋白(AOD)水平分别为(0.8±0.2)和(0.4±0.1),显著高于非显著炎症患者[分别为(0.3±0.1)和(0.1±0.0),P<0.05];48例显著肝纤维化组肝组织LXRα mRNA和其蛋白(AOD)水平分别为(0.7±0.2)和(0.3±0.1),显著高于70例非显著肝纤维化患者[分别为(0.3±0.1)和(0.1±0.1),P<0.05],CYP7A1 mRNA和其蛋白(AOD)水平分别为(0.7±0.2)和(0.3±0.1),显著高于非显著肝纤维化患者[分别为(0.4±0.2)和(0.2±0.1),P<0.05]。结论 LXRα和CYP7A1表达上调可能参与了CHB患者肝组织炎症和肝纤维化发生发展过程,其机制值得进一步研究。  相似文献   
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《Vaccine》2022,40(19):2679-2695
Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.  相似文献   
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目的:探讨miRNA调控食管癌细胞CaES-17的凋亡和增殖的潜在机制。方法:纳入2019年06月至2020年06月在我院接受治疗的食管癌患者6例,采集其食管癌组织和癌旁组织后抽取总RNA进行miRNA高通量测序。在食管癌细胞CaES-17中过表达食管癌组织和癌旁组织中的差异miRNA,检测食管癌细胞CaES-17的凋亡和增殖情况。通过TargentScan7.2在线分析和荧光素酶报告实验分析miRNA的靶标mRNA。结果:6例患者的食管癌组织和癌旁组织通过高通量测序发现hsa-miR-30d-5p、hsa-miR-6818-5p、hsa-miR-525-5p、hsa-miR-1909-3p、hsa-miR-212-5p、hsa-miR-586、hsa-miR-1286、hsa-miR-365b-3p、hsa-miR-30e-5p、hsa-miR-4317在食管癌组织和癌旁组织中的表达差异在8倍以上,并且食管癌组织均高于癌旁组织。干扰上述miRNA后,发现干扰miR-586能够抑制食管癌细胞CaES-17的增殖水平和迁移水平,提高凋亡水平。过表达miR-586后,食管癌细胞CaES-17的凋亡水平下降,增殖水平和迁移水平上升。TargentScan7.2在线分析和荧光素酶报告实验发现miR-586靶向TLR7的3' 端非编码区。敲低TLR7后,食管癌细胞CaES-17的凋亡水平下降,增殖水平和迁移水平上升。过表达TLR7后,食管癌细胞CaES-17的凋亡水平上升,增殖水平和迁移水平下降。但是,同时干扰miR-586和敲低TLR7后,相比于对照食管癌细胞,食管癌细胞CaES-17的凋亡水平和增殖水平无显著差异。结论:miR-586通过靶向TLR7的3' 端非编码区,降解了TLR7的mRNA,抑制了TLR7的蛋白翻译,最终抑制了食管癌细胞CaES-17的凋亡、促进了食管癌细胞CaES-17的增殖。  相似文献   
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《Immunobiology》2022,227(6):152298
PLPPs (Phospholipid phosphatases) are widely expressed in different human tissues, regulate cell signal transduction, and are overexpressed in cancers such as gliomas, pancreatic adenocarcinoma, lung adenocarcinoma, and so on. As a member of the PLPP family, PLPP2 (phospholipid phosphatase 2) plays a vital role in the occurrence and development of breast cancer, but its mechanism is still unclear. Our research found that PLPP2 was overexpressed in breast cancer, and the higher expression level of PLPP2 showed a worse prognosis for breast cancer patients. Further analysis showed that overexpression of PLPP2 affected the expression of CDC34 (cell-division cycle 34), LSM7 (Like-Smith 7), and SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) through EMT (epigenetic-mesenchymal transition) related pathways to promote the occurrence and development of breast cancer. In vitro, silencing PLPP2 significantly reduced the proliferation, invasion, and migration abilities of human breast cancer cells MDA-MB-231. ER+ is a common subtype of breast cancer. Furthermore, we found that the overexpression of PLPP2 was significantly related to the poor prognosis of ER+ breast cancer. These results indicate that PLPP2 has value as a potential therapeutic target for breast cancer, especially for ER+ breast cancer.  相似文献   
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Cancer is one of the leading causes of death in the world. Efforts to find and develop cancer drugs from natural products continue with the exploration of trisindoline, a substance that is isolated from marine sponges Hyrtios altum. Trisindoline is an indole trimer alkaloid compound that has been successfully synthesized into trisindoline 1, 3 and 4. Trisindoline is cytotoxic in cell lines and in this study, trisindoline was able to induce apoptosis in the in silico and in vitro tests that were carried out. The in silico test was carried out through molecular docking using the Autodock Vina method and the Molecular Dynamics (MD) Simulation QM / MM AMBER. The target proteins used were protein p53 and caspase ?9 which played a role in the apoptotic pathway and cyclin D1 which played a role in cell proliferation. Meanwhile, cytotoxicity analysis was carried out using the MTT method (3- (4,5-dimethyltiazol ?2-yl) ?2,5 -dipenyl tetrazolium bromide). Nevertheless, the ability of trisindoline to induce phagocytosis is still unrevealed. The phagocytosis assay was carried out by assessing the macrophage capacity and phagocytic index using the latex-beads model. The in silico results showed that the binding affinity values between the target protein Cdk-2 and the trisindoline 1, trisindoline 3 and trisindoline 4 ligands were ?7.3 kcal / mol, ?7.7 kcal / mol and ?6.6 kcal / mol respectively. The binding affinity values between the target protein p53 and the trisindoline 1, trisindoline 3 and trisindoline 4 ligands were ?7.5 kcal / mol, ?7.4 kcal / mol and ?7.5 kcal / mol respectively. The binding affinity values between the target protein caspase-9 and the trisindoline 1, trisindoline 3 and trisindoline 4 ligands were ?7.5 kcal / mol, ?7.1 kcal / mol and ?7.2 kcal / mol respectively. The results of RMSD (Root Mean Square Deviation), RMSF (Root Mean Square Fluctuation), and hydrogen bonds in the MD (Molecular Dynamics) Simulation showed that Cdk-2 formed a protein complex with trisindoline 3, protein p53 with trisindoline 1 and caspase-9 with trisindoline 1. The cytotoxicity assay was carried out in the MCF-7 cell line and the IC50 value obtained for trisindoline 1 was 2.059 μM, for trisindoline 3 was 3.9759 ??μM, for trisindoline 4 was 15.46 μM and for doxorubicin was 9.88 μM. Furthermore, the phagocytosis test was carried out using trisindoline 1, 3 and 4. Our results showed that 6.25 µg mL?1 of trisindoline 1 and trisindoline 3 were able to induce the phagocytosis capacity of macrophage cells of 38.34; whereas trisindoline 4 at a concentration of 50 µg mL?1 induces a phagocytosis capacity of 32.89. Trisindoline 1, 3 and 4 showed potentials of immunostimulants at low concentrations but showed potentials of immunosuppressants at high concentrations. The overall results demonstrated that trisindoline 1 and 3 are potential anti-cancer candidates capable of activating the apoptotic pathway.  相似文献   
7.
Defects of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein affect the homeostasis of chloride, bicarbonate, sodium, and water in the airway surface liquid, influencing the mucus composition and viscosity, which induces a severe condition of infection and inflammation along the whole life of CF patients. The introduction of CFTR modulators, novel drugs directly intervening to rescue the function of CFTR protein, opens a new era of experimental research. The review summarizes the most recent advancements to understand the characteristics of the infective and inflammatory pathology of CF lungs.  相似文献   
8.
目的:建立HPLC一测多评法同时测定胃疡灵颗粒中肉桂酸、桂皮醛、毛蕊异黄酮葡萄糖苷、芒柄花苷、芒柄花素、6-姜辣素、8-姜酚和10-姜酚的含量。方法:采用HPLC法,以Agilent SB-C18柱(250 mm×4.6 mm,5μm)为色谱柱,流动相A为乙腈-甲醇(9∶1),流动相B为0.1%磷酸溶液,梯度洗脱(0~13 min,28%A;13~24 min,28%→35%A;24~39 min,35%→56%A;39~53 min,56%→85%A;53~60 min,85%→28%A),流速为1.1 ml/min,检测波长为280 nm,柱温为25℃。以毛蕊异黄酮葡萄糖苷为内参物,建立其他7个成分的相对校正因子,计算各成分含量。结果:肉桂酸、桂皮醛、毛蕊异黄酮葡萄糖苷、芒柄花苷、芒柄花素、6-姜辣素、8-姜酚和10-姜酚分别在0.59~11.80、7.47~149.40、2.18~43.60、1.91~38.20、4.49~89.80、3.87~77.40、0.94~18.80、1.46~29.20μg/ml(r≥0.9991)范围内线性关系良好;平均加样回收率分别为(96.89±1.04)%、(100.05±0.64)%、(99.52±1.18)%、(98.51±1.30)%、(99.38±0.77)%、(98.29±0.88)%、(97.72±1.26)%和(97.93±1.01)%(n=9);肉桂酸、桂皮醛、芒柄花苷、芒柄花素、6-姜辣素、8-姜酚和10-姜酚的相对校正因子分别为0.8263、0.8490、0.9720、1.2005、1.2766、0.7202和0.8749,一测多评法计算值和外标法实测值无明显差异。结论:本研究建立的HPLC一测多评法操作便捷、结果准确,可用于胃疡灵颗粒的质量控制。  相似文献   
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AimTo determine whether convalescent angiotensin (1?7) peptide replacement therapy with plasma (peptide plasma) transfusion can be beneficial in the treatment of critically ill patients with severe coronavirus 2 (SARS-CoV-2) infection.Study designCase series of 9 critically ill patients with laboratory-confirmed COVID-19 who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment.Peptide plasma: Plasma with angiotensin (1?7) content 8–10 times higher than healthy plasma donors was obtained from suitable donors. Peptide plasma transfusion was applied to 9 patients whose clinical status and/or laboratory profile deteriorated and who needed intensive care for 2 days.ResultsIn our COVID-19 cases, favipiravir, low molecular weight heparin treatment, which is included in the treatment protocol of the ministry of health, was started. Nine patients with oxygen saturation of 93% and below despite nasal oxygen support, whose clinical and/or laboratory deteriorated, were identified. The youngest of the cases was 36 years old, and the oldest patient was 85 years old. 6 of the 9 cases had male gender. 3 cases had been smoking for more than 10 years. 4 cases had at least one chronic disease.In all of our cases, SARS CoV2 lung involvement was bilateral and peptide plasma therapy was administered in cases when oxygen saturation was 93% and below despite nasal oxygen support of 5 liters/minute and above, and intensive care was required. Although it was not reflected in the laboratory parameters in the early period, 8 patients whose saturations improved with treatment were discharged without the need for intensive care. However, a similar response was not obtained in one case. Oxygen requirement increased gradually and, he died in intensive care process. An increase of the platelet count was observed in all cases following the peptide plasma treatment.ConclusionIn this preliminary case series of 9 critically ill patients with COVID-19, administration of plasma containing angiotensin (1?7) was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.  相似文献   
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