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991.
目的探究miR-150-5p靶向SIRT1提高肝癌细胞放射敏感性的作用机制。方法用分次放疗放射递增法诱导建立放射抵抗型细胞株(RR-HepG2);RT-qPCR检测HepG2和RR-HepG2在不同放射剂量下miR-150-5p的表达水平;细胞克隆实验检测相同放射剂量下两种细胞的放疗敏感性;流式细胞计量术和Western blot检测过表达miR-150-5p对HepG2凋亡的影响;双荧光素酶报告基因法检测miR-150-5p与SIRT1的关联;细胞克隆实验和Western blot检测过表达SIRT1后,细胞的放疗敏感性和凋亡蛋白的变化。结果与亲代HepG2比较,相同放射剂量下,RRHepG2组miR-150-5p的表达量均显著降低(P<0. 05);放射处理后,与control、agomiR-NC组比较,agomiR-150-5p组的细胞存活分数显著降低,敏感性高(P<0. 05),Bax、caspase-9蛋白表达水平显著升高,Bcl-2蛋白表达水平显著降低,细胞凋亡率显著升高;双荧光素酶报告基因法验证miR-150-5p靶向调控SIRT1。与agomiR-NC组比较,野生型(WT) agomiR-150-5p荧光素酶活性显著降低,SIRT1蛋白水平显著降低(P<0. 05);与anta-agomiR-NC比较,野生型(WT) anta-agomiR-150-5p荧光素酶活性显著升高,SIRT1蛋白水平显著升高(P<0. 05);放射处理后,与agomiR-NC组比较,agomiR-150-5p组的细胞存活分数显著降低,Bax、caspase-9蛋白表达水平显著升高,Bcl-2蛋白表达水平显著降低(P<0. 05);与agomiR-150-5p+vector组比较,agomiR-150-5p+SIRT1组的细胞存活分数显著升高,Bax、caspase-9蛋白表达水平显著降低,Bcl-2蛋白表达水平显著升高(P<0. 05)。结论 miR-150-5p靶向SIRT1,下调其表达,提高肝癌细胞放射敏感性,可为临床肝癌放射治疗增敏提供靶点。 相似文献
992.
Andrea Biloglav Linda Olsson‐Arvidsson Johan Theander Mikael Behrendtz Anders Castor Bertil Johansson 《Genes, chromosomes & cancer》2020,59(9):540-543
In recent years, a subgroup of B‐cell precursor acute lymphoblastic leukemia (BCP ALL) without an established abnormality (“B‐other”) has been shown to be characterized by rearrangements of ABL1, ABL2, CSF1R, or PDGFRB (a.k.a. ABL‐class genes). Using FISH with probes for these genes, we screened 55 pediatric and 50 adult B‐other cases. Three (6%) of the adult but none of the childhood B‐other cases were positive for ABL‐class aberrations. RT‐PCR and sequencing confirmed a rare SFPQ‐ABL1 fusion in one adult B‐other case with t(1;9)(p34;q34). Only six SFPQ‐ABL1‐positive BCP ALLs have been reported, present case included. A review of these shows that all harbored fusions between exon 9 of SFPQ and exon 4 of ABL1, that the fusion is typically found in adolescents/younger adults without hyperleukocytosis, and that IKZF1 deletions are recurrent. The few patients not treated with tyrosine kinase inhibitors (TKIs) and/or allogeneic stem cell transplantation relapsed, strengthening the notion that TKI should be added to the therapy of SFPQ‐ABL1‐positive BCP ALL. 相似文献
993.
Cristina Fortuno Jessica Mester Tina Pesaran Jeffrey N. Weitzel Jill Dolinsky Amal Yussuf Kelly McGoldrick Judy E. Garber Sharon A. Savage Payal P. Khincha D. Gareth Evans Maria Isabel Achatz Kim E. Nichols Kara N. Maxwell Joshua D. Schiffman Renata Sandoval Paul A. James Amanda B. Spurdle 《Human mutation》2020,41(9):1555-1562
994.
Zili Zhang Jian Wang Zeguang Zheng Xindong Chen Guihua Xu Sifan Chen Fei Liu Lingdan Chen Mingjing Ding Liang Yuan Yuanyuan Li Jing Qian Xiaohui Xie Bingxian Deng Wenju Lu 《Human mutation》2020,41(7):1280-1297
The aberrant expression of matrix metalloproteinases (MMPs) is known to contribute to the pathogenesis of airway remodeling and alveolar disruption in chronic obstructive pulmonary disease (COPD). In the discovery stage, 11 COPD from five families were subjected to whole‐genome sequencing, and 21 common polymorphisms in MMPs and TIMPs were identified. These polymorphisms were genotyped in two subsequent verification studies. Of these polymorphisms, c.2392G>A (rs2664370T>C) and c.4158C>A (rs2664369T>G) in MMP16 remained significantly different. Functionally, we found that MMP16 expression was significantly increased in peripheral blood monocytes (PBMCs) from COPD and in cigarette smoke extract‐treated 16HBE cells compared with controls. This was also shown by bioinformatics analysis. COPD carrying rs2664370CC showed decreased levels of MMP16 in the plasma and in PBMCs compared with those carrying CT and TT. Treatment with hsa‐miR‐576‐5p mimics led to a greater reduction in luciferase reporter activity in cells transfected with rs2664370CC. Moreover, blood levels of base excess, PCO2, and PO2 in COPD with rs2664370CC were significantly lower than those with rs2664370CT+TT. Taken together, these results demonstrate that the rs2664370T>C polymorphism in MMP16 protects against the risk of COPD, likely by favoring interaction with hsa‐miR‐576‐5p, leading to reduced MMP16 expression and improved blood gas levels. 相似文献
995.
996.
Mariyo Rokutan‐Kurata Sachiko Minamiguchi Tatsuki R Kataoka Kaoru Abiko Masaki Mandai Hironori Haga 《Pathology international》2020,70(7):413-421
Immunohistochemically p16 (CDKN2A)‐negative uterine cervical squamous cell carcinoma (SCC) is uncommon, and there are few reports about its pathological features. This study explored the causes of p16 negativity in such cases. We analyzed diagnostic tissue samples of five cases of p16‐negative cervical SCC among 107 patients who underwent hysterectomy at Kyoto University Hospital between January 2010 and December 2015. The samples were subjected to immunohistochemical staining, in situ hybridization and a genetic analysis. Two of five cases were positive for human papilloma virus (HPV) by genotyping. One was positive for HPV56 with promoter hypermethylation of CDKN2A and co‐existing Epstein–Barr virus infection. Another was positive for HPV6 categorized as low‐risk HPV with condylomatous morphology. Among the remaining three cases, one had amplification of the L1 gene of HPV with promoter hypermethylation of CDKN2A and TP53 mutation, and one of the other two HPV‐negative cases had a homozygous CDKN2A deletion, while the other was positive for p53 and CK7. p16‐negativity of cervical SCC is often associated with an unusual virus infection status and CDKN2A gene abnormality. 相似文献
997.
Ruili Wang Qing Li Ya He Ying Yang Qiaoya Ma Chen Li 《Genes to cells : devoted to molecular & cellular mechanisms》2020,25(6):364-374
Microglial inflammation is identified as a key process associated with Parkinson's disease (PD) pathogenesis. Our previous study showed that miR‐29c‐3p (miR‐29c) exhibited anti‐inflammatory properties in PD animal and neuronal models. However, the specific role and regulatory mechanism of miR‐29c played in microglia are still unclear. In this study, lipopolysaccharide (LPS)‐stimulated BV‐2 cells were used to establish a cellular model of microglial activation for investigating PD. The results showed a decreased expression of miR‐29c in LPS‐induced BV‐2 cells. Over‐expression of miR‐29c suppressed LPS‐triggered Iba‐1 increment, pro‐inflammatory cytokine release, and NF‐кB and TXNIP/NLRP3 inflammasome activation. Silence of miR‐29c induced similar effects with LPS on microglial inflammation. In addition, we found that NFAT5 was negatively correlated with miR‐29c. Knockdown of NFAT5 blocked the aggravated inflammation in microglia treated by miR‐29c inhibitor. Thus, these findings suggest that miR‐29c modulates NLRP3 inflammasome to impair microglial inflammatory responses by targeting NFAT5, which represents a promising therapeutic target for PD. 相似文献
998.
《European journal of medical genetics》2020,63(4):103843
We identified a de novo 44.7 Kb interstitial 12p13.33 micro-deletion that involves solely the first exon of the CACNA1C (MIM 114205), using microarray-based comparative genomic hybridization (aCGH). The associated main phenotype is characterized by expressive language impairment, tremors, fine motor-skills delay, muscular hypotonia, and joint laxity. A careful comparison between the clinical and genomic characteristics between our proband and 20 previously reported patients, led us to propose CACNA1C haploinsufficiency as the main cause of both expressive language delay and motor-skills impairment. Pathogenic variants of CACNA1C have been associated to a plethora of clinical phenotypes, such as Timothy syndrome (TS, OMIM 601005), Brugada syndrome (BRGDA3, OMIM 611875) and a variety of neuropsychiatric disorders (bipolar disorder, major depression, schizophrenia, autism spectrum disorder, psychotic manifestations). In this report we describe a 12p13.33 micro-deletion involving one coding gene only, in contrast with previous studies that mostly concluded that a multi-genes deletion in the 12p13.33 sub-telomeric region is responsible of the minimum clinical phenotype of patients with 12p13.33 monosomy. Certainly, larger deletions spanning multiple Mb in 12p13.33 are responsible for more severe phenotypes, associated to a variable degree of dysmorphic features. 相似文献
999.
1000.
Alpinumisoflavone (AIF) as a principal active ingredient of traditional Chinese herb Derris eriocarpa exerts a broad spectrum of anticancer activities against solid tumors. However, little is known about the effect of AIF on papillary thyroid cancer (PTC). Objectives of this study are to investigate the effect of AIF on cell growth, apoptosis, and metastasis of PTC cells and uncover its underlying mechanisms. Results showed that AIF treatment notably suppressed cell viability, migration, invasion, and epithelial–mesenchymal transition (EMT) process, as well as induced apoptotic cell death. In addition, microarray analysis results revealed that miR-141-3p level was dramatically elevated upon AIF insulation, suggesting that miR-141-3p may mediate the suppressive role of AIF against PTC. Moreover, miR-141-3p knockdown effectively reversed the effects of AIF on cell growth, migration, invasion, and EMT, while promoted PTC cell apoptosis escape. Furthermore, in vivo findings also confirmed that the antigrowth and antimetastasis activities of AIF were, at least partly, mediated by upregulation of miR-141-3p. Overall, AIF could serve as a potential anticancer compound for PTC treatment. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1842–1850, 2020. © 2019 American Association for Anatomy 相似文献