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1.
目的 考察香菇多糖–番荔素纳米粒的性能,及其对小鼠黑色素瘤肺转移癌的体内外抑制效果。方法 采用反溶剂沉淀法制备香菇多糖–番荔素纳米粒,以动态光散射法测定粒径、分散系数(PDI)及Zeta电位,及其在不同生理介质(5%的葡萄糖、生理盐水、PBS的混悬液)中的稳定性;采用透射电子显微镜观察纳米粒的形态、大小;精确称量香菇多糖–番荔素纳米粒质量,并采用HPLC法测量番荔素中番荔辛,计算载药量;用酶标仪在540 nm处测量不同浓度(2、1.5、1、0.5、0.25、0.125 mg/mL)香菇多糖–番荔素纳米粒与5%葡萄糖溶液等渗液的吸光度,并计算溶血率;采用透析袋法考察香菇多糖–番荔素纳米粒的体外释放行为。用划痕实验与MTT实验对香菇多糖–番荔素纳米粒进行体外药效学考察。构建黑色素瘤肺转移癌小鼠模型,以紫杉醇注射液为阳性对照,对不同剂量香菇多糖–番荔素纳米粒进行体内药效学研究。结果 香菇多糖–番荔素纳米粒的粒径为(160.6±1.0)nm,PDI为0.082±0.023,Zeta电位为(-28.10±1.14)mV,透射电镜下呈球状。香菇多糖–番荔素纳米粒在5%的葡萄糖、血浆中稳定,无溶血现象;在体外可持续缓慢释放。体外研究结果显示,与番荔素原料药相比,香菇多糖–番荔素纳米粒对黑色素瘤B16F10细胞的迁移抑制作用及细胞毒性显著增加。体内药效学结果显示,香菇多糖–番荔素纳米粒iv给药14 d后,香菇多糖–番荔素纳米粒0.4 mg/mL组对黑色素瘤肺部转移抑制率可达到91.6%,S-100蛋白的表达也较模型组明显下调。结论 香菇多糖可作为稳定剂制备香菇多糖–番荔素纳米粒,香菇多糖–番荔素纳米粒对黑色素瘤肺转移癌初期具有显著的抑制作用。  相似文献   
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目的 探索阿柏西普对葡萄膜黑色素瘤细胞的作用及其机制。方法 将B16F10细胞(葡萄膜黑色素瘤细胞)分为实验组和对照组,对照组不使用药物处理,实验组分别用0.2 g·L-1、2.0 g·L-1、4.0 g·L-1阿柏西普进行干预。通过实时细胞电子分析系统(RT-CES)、CCK-8法探讨不同剂量的阿柏西普对葡萄膜黑色素瘤细胞生长过程的影响;ELISA分析阿柏西普对葡萄膜黑色素瘤细胞中VEGF-A含量的影响;RT-PCR检测不同剂量阿柏西普对葡萄膜黑色素瘤细胞VEGF-A mRNA表达的影响;流式细胞仪分析不同剂量阿柏西普对葡萄膜黑色素瘤细胞周期和凋亡的影响。结果 0.2 g·L-1、2.0 g·L-1、4.0 g·L-1的阿柏西普作用B16F10细胞 24 h 后,细胞存活率分别下降至(95.10±1.76)%、(87.33±2.20)%和(74.36±1.67)%。RT-PCR检测结果显示:阿柏西普能够下调细胞中VEGF-A mRNA的表达;ELISA检测结果表明,阿柏西普可抑制细胞中VEGF-A的水平,其中4.0 g·L-1阿柏西普抑制作用最为明显。此外,与对照组[细胞凋亡率0%,G1期细胞比例为(27.60±0.36)%]相比,0.2 g·L-1、2.0 g·L-1、4.0 g·L-1阿柏西普干预24 h后,B16F10细胞凋亡率分别升高为3.51%、11.10%和14.77%,G1期细胞比例分别升高至(64.09±0.34)%、(66.02±0.65)%、(67.49±0.33)%,差异均有统计学意义(均为P<0.05)。结论 阿柏西普对葡萄膜黑色素瘤细胞有显著抑制作用,其作用机制为抑制细胞中VEGF-A水平,从而诱导细胞发生凋亡和S期阻滞,其作用具有浓度依赖性。  相似文献   
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Malignant melanoma (MM) is a highly aggressive neoplasm with a growing worldwide incidence. It is not uncommon that the disease is already metastatic at the time of the first diagnosis. Regional lymph nodes and skin are the first and most common metastatic sites, followed by distant visceral sites (lungs, liver, and central nervous system) and bone. In this clinical setting, fine-needle aspiration (FNA) often represents the first diagnostic approach. FNA is a useful tool to obtain a rapid and accurate diagnosis, in conjunction with ancillary techniques and molecular analysis, as recommended by recent guidelines. The aim of this review was to describe the cytomorphology, immunocytochemical tools, and molecular tools used for the diagnosis of MM metastases on FNA.  相似文献   
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ObjectiveTo observe the relationship between the different stages of type 2 diabetes mellitus (T2DM) and the intestinal flora and verify its underlying mechanism.MethodsT2DM rats were generated by high-fat diet (HFD) combined with intraperitoneal streptozotocin (STZ) injection. The rats were divided into four groups: the control group (fed with normal feed for 1 month), the HFD group (fed with HFD for 1 month), the T2DM group (HFD combined with STZ and blood glucose ≥11.1 mM), and the unformed T2DM model (Un-mod) group (HFD combined with STZ and blood glucose <11.1 mM). Feces were collected, and bacterial communities in the fecal samples were analyzed by 16S rRNA gene sequencing. The content of short-chain fatty acids (SCFAs) in feces was measured by gas chromatography. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of G protein-coupled receptor 41 (GPR41) and GPR43.ResultsAt different stages of T2DM, the intestinal flora and SCFAs content of rats were significantly decreased (all P < .05). Our results indicated that g__Prevotella had a significant negative correlation, and g__Ruminococcus_torques_group and g__lachnoclastic had a significant positive correlation with blood glucose. The content of SCFAs, in particular acetate and butyrate, in rat feces of different stages of T2DM were significantly reduced, as well as GPR41 and GPR43 expression. The results in the Un-mod group were similar to the T2DM group, and the expression of GPR41 and GPR43 proteins were significantly higher than those in the T2DM group (both P < .001).ConclusionThe intestinal flora–SCFAs–GPR41/GPR43 network may be important in the development of T2DM. Decreasing blood glucose levels by regulating the intestinal flora may become a new therapeutic strategy for T2DM, which has very important clinical and social values.  相似文献   
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PurposeTo report the 5-year results from the Pivotal Multicenter Trial of Ultrasound-Guided Percutaneous Arteriovenous Fistula (pAVF) Creation for Hemodialysis Access.Materials and MethodsThe retrospective review of 107 intent-to-treat (ITT) patients from the pivotal trial provided a long-term follow-up population (LTP) of 85 patients with a median follow-up duration of 50 months (range, 12–60 months). Data evaluated in the LTP group were fistula maturation and usage, secondary procedures, and complications. The Kaplan-Meier analysis of primary patency, assisted primary patency, cumulative patency, and functional patency (time from 2-needle cannulation to abandonment) were performed for the ITT population.ResultsIn the LTP, 99% (84 of 85) of fistulae were mature, with 99% (78 of 79) of patients requiring hemodialysis using their pAVF. Sustained fistula use (2-needle cannulation at the prescribed rate, 2 of 3 sessions) was achieved in 92% (78 of 85) of patients, with 7 patients not using their pAVF because they were not on dialysis (n = 4), were on peritoneal dialysis (n = 2), and refused to use fistula (n = 1). Fistula maintenance was required in 31.8% (27 of 85) of patients and included fistula dysfunction (21.2%), thrombosis (5.9%), cannulation injury (12.9%), and arm swelling (4.7%). The number of procedures performed per patient per year to maintain function and patency was 0.32 (91 of 288) for years 2–5. The cumulative patency rates were 89.5%, 88.4%, 88.4%, 85.6%, and 82.0% for years 1, 2, 3, 4, and 5, respectively. The functional patency was 91.8% at the end of the study. There were no major complications related to pAVF during the long-term follow-up.ConclusionsPercutaneous fistulae have provided clinically effective and durable access for hemodialysis with low complications. The continued use and evaluation of pAVF are warranted.  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   
8.
《Molecular therapy》2022,30(8):2844-2855
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目的 了解长沙地区无偿献血人群隐匿性乙型肝炎病毒感染(occult hepatitis B virus infection,OBI)流行情况,探讨HBV基因型分布特征和S区氨基酸突变的情况。方法 对长沙地区检测结果为HBsAg-/HBV DNA+的无偿献血血液样本进行HBV血清标志物检测,对其中的OBI样本进行HBV病毒载量检测和S区基因扩增,分析血清学标志物抗HBs与病毒载量检出与否的关系,并对扩增产物进行HBV基因分型和突变位点分析。结果 2019年1月—2020年1月长沙地区173 893份无偿献血标本共确认58例OBI样本,OBI流行率为0.033%;共发现7种血清学模式,抗HBc单独阳性最多,占38.98%,所有样本中抗HBc阳性率为89.83%;16例样本能检测出病毒载量,其中14例样本浓度小于100 IU/ml;抗HBs阳性组和阴性组间的病毒载量检出率无统计学差异;75.0%(12/16)样本扩增出S区序列,基因型均为B型,均发生突变,其中11例的HBsAg抗原决定簇及周边主要亲水区域(major hydrophilic region, MHR)发生氨基酸突变。结论 长沙地区无偿献血者中的OBI感染率在全国属于偏低水平;HBV基因型主要是B型,MHR区的氨基酸突变可能是造成OBI的原因,突变有本地特点。  相似文献   
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