全文获取类型
收费全文 | 41080篇 |
免费 | 2715篇 |
国内免费 | 156篇 |
专业分类
耳鼻咽喉 | 517篇 |
儿科学 | 1038篇 |
妇产科学 | 830篇 |
基础医学 | 6180篇 |
口腔科学 | 3924篇 |
临床医学 | 3246篇 |
内科学 | 8309篇 |
皮肤病学 | 912篇 |
神经病学 | 3181篇 |
特种医学 | 857篇 |
外国民族医学 | 1篇 |
外科学 | 4524篇 |
综合类 | 383篇 |
一般理论 | 11篇 |
预防医学 | 4681篇 |
眼科学 | 503篇 |
药学 | 3022篇 |
中国医学 | 409篇 |
肿瘤学 | 1423篇 |
出版年
2023年 | 360篇 |
2022年 | 959篇 |
2021年 | 1520篇 |
2020年 | 1035篇 |
2019年 | 1335篇 |
2018年 | 1583篇 |
2017年 | 1185篇 |
2016年 | 1195篇 |
2015年 | 1454篇 |
2014年 | 1830篇 |
2013年 | 2185篇 |
2012年 | 3340篇 |
2011年 | 3667篇 |
2010年 | 1933篇 |
2009年 | 1454篇 |
2008年 | 2418篇 |
2007年 | 2336篇 |
2006年 | 2071篇 |
2005年 | 1726篇 |
2004年 | 1500篇 |
2003年 | 1325篇 |
2002年 | 1154篇 |
2001年 | 794篇 |
2000年 | 829篇 |
1999年 | 652篇 |
1998年 | 229篇 |
1997年 | 162篇 |
1996年 | 155篇 |
1995年 | 141篇 |
1994年 | 129篇 |
1993年 | 98篇 |
1992年 | 291篇 |
1991年 | 281篇 |
1990年 | 247篇 |
1989年 | 237篇 |
1988年 | 221篇 |
1987年 | 165篇 |
1986年 | 159篇 |
1985年 | 153篇 |
1984年 | 124篇 |
1983年 | 108篇 |
1979年 | 109篇 |
1978年 | 87篇 |
1975年 | 66篇 |
1974年 | 72篇 |
1973年 | 78篇 |
1970年 | 75篇 |
1969年 | 62篇 |
1968年 | 69篇 |
1967年 | 63篇 |
排序方式: 共有10000条查询结果,搜索用时 17 毫秒
991.
Marianna Agudelo Martin Palus Jennifer R. Keeffe Filippo Bianchini Pavel Svoboda Jií Salt Avery Peace Anna Gazumyan Melissa Cipolla Tania Kapoor Francesca Guidetti Kai-Hui Yao Jana Elsterov Dana Teislerov Ale Chrdle Vclav Hnig Thiago Oliveira Anthony P. West Jr. Yu E. Lee Charles M. Rice Margaret R. MacDonald Pamela J. Bjorkman Daniel Rek Davide F. Robbiani Michel C. Nussenzweig 《The Journal of experimental medicine》2021,218(5)
Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC50s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI–EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV. 相似文献
992.
Andressa P. Oliveira Fernando M. Simabuco Rodrigo E. Tamura Manuel C. Guerrero Paulo G.G. Ribeiro Towia A. Libermann Luiz F. Zerbini Armando M. Ventura 《Virus research》2013
Characterization of Human Respiratory Syncytial Virus (HRSV) protein interactions with host cell components is crucial to devise antiviral strategies. Viral nucleoprotein, phosphoprotein and matrix protein genes were optimized for human codon usage and cloned into expression vectors. HEK-293T cells were transfected with these vectors, viral proteins were immunoprecipitated, and co-immunoprecipitated cellular proteins were identified through mass spectrometry. Cell proteins identified with higher confidence scores were probed in the immunoprecipitation using specific antibodies. The results indicate that nucleoprotein interacts with arginine methyl-transferase, methylosome protein and Hsp70. Phosphoprotein interacts with Hsp70 and tropomysin, and matrix with tropomysin and nucleophosmin. Additionally, we performed immunoprecipitation of these cellular proteins in cells infected with HRSV, followed by detection of co-immunoprecipitated viral proteins. The results indicate that these interactions also occur in the context of viral infection, and their potential contribution for a HRSV replication model is discussed. 相似文献
993.
André F. Pastor Laís Rodrigues Moura José W.D. Neto Eduardo J.M. Nascimento Carlos E. Calzavara-Silva Ana Lisa V. Gomes Ana Maria da Silva Marli T. Cordeiro Ulisses Braga-Neto Sergio Crovella Laura H.V.G. Gil Ernesto T.A. Marques Jr. Bartolomeu Acioli-Santos 《Human immunology》2013
Four genetic polymorphisms located at the promoter (C-257T) and coding regions of CFH gene (exon 2 G257A, exon 14 A2089G and exon 19 G2881T) were investigated in 121 dengue patients (DENV-3) in order to assess the relationship between allele/haplotypes variants and clinical outcomes. A statistical value was found between the CFH-257T allele (TT/TC genotypes) and reduced susceptibility to severe dengue (SD). Statistical associations indicate that individuals bearing a T allele presented significantly higher protein levels in plasma. The −257T variant is located within a NF-κB binding site, suggesting that this variant might have effect on the ability of the CFH gene to respond to signals via the NF-κB pathway. The G257A allelic variant showed significant protection against severe dengue. When CFH haplotypes effect was considered, the ancestral CG/CG promoter-exon 2 SNP genotype showed significant risk to SD either in a general comparison (ancestral × all variant genotypes), as well as in individual genotypes comparison (ancestral × each variant genotype), where the most prevalent effect was observed in the CG/CG × CA/TG comparison. These findings support the involvement of −257T, 257A allele variants and haplotypes on severe dengue phenotype protection, related with high basal CFH expression. 相似文献
994.
Patricia C. Grenzi Renato de Marco Rosemeire Z.R. Silva Érika F. Campos Maria Gerbase-DeLima 《Human immunology》2013
False-positive anti-HLA reactions may occur in Luminex-single antigen (SA) beads assays, and it is important to recognize them to correctly interpret the test. The purpose of this report is to describe a peculiar pattern of reactivity, characterized by positivity with beads coated with HLA-DRB1∗09:01, DRB3∗01:01, DRB3∗02:02, DRB3∗03:01, DPB1∗02:01, DPB1∗20:01 and DPB1∗28:01, that was observed in 141 of 8121 serum samples tested in our laboratory with three different lots of the same kit (LABScreen® SA, One Lambda). These 141 serum samples came from 56 different patients on the kidney transplant waiting list, corresponding to 1% of the patients. Of these, 10 males had never been transfused or transplanted. About 66% of the patients had positive reactions against self-antigen HLA-DRB3 alleles. No reactions against native HLA-DRB1∗09:01 were observed in flow cytometry crossmatch and in absorption/elution experiments, leading to the conclusion that the reactivity was due to antibodies against epitopes present in denatured forms of HLA-class II antigens. The occurrence of this reactivity pattern was associated with female gender and systemic lupus erythematosus (SLE). 相似文献
995.
996.
Larissa Mesquita Nunes Flávio Monteiro Ayres Isadora Carvalho Medeiros Francescantonio Vera Aparecida Saddi Melissa Ameloti Gomes Avelino Rita de Cássia Gonçalves Alencar Rosana Correa da Silva Alexandre J. Meneghini Isabela Jubé Wastowski 《Human immunology》2013
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and can present as lymph node metastasis in 30 to 65% of cases when initially diagnosed. High frequency recurrence, distant metastasis and treatment resistance can be found in cases of PTC so early diagnosis and treatment are critical for improved prognosis and better survival rates. The characterization of new biomarkers has proved useful for the diagnosis and follow-up of these patients. HLA-G is a non-classical HLA class I molecule whose expression in cancer cells has been associated with tumor evasion of immune response. Therefore, the aim of this study was to investigate the HLA-G expression and its clinical significance in PTC. Paraffin-embedded thyroid biopsies of 70 PTC patients (40 of whom had presented with metastasis) were evaluated. HLA-G-staining was observed in tumor cells in PTC, and the HLA-G expression was significantly associated with an increased occurrence of lymph node metastasis (p = 0.0006) and capsular invasion (p = 0.02). This preliminary data shows the HLA-G expression in thyroid carcinoma specimens for the first time and suggests that this expression could impair efficient anti-tumor immunity in PTC. This would indicate that HLA-G could have an independent prognostic value in PTC, principally for tumor recurrence. 相似文献
997.
Rodney A. Rosalia Esther D. Quakkelaar Anke Redeker Selina Khan Marcel Camps Jan W. Drijfhout Ana Luisa Silva Wim Jiskoot Thorbald van Hall Peter A. van Veelen George Janssen Kees Franken Luis J. Cruz Angelino Tromp Jaap Oostendorp Sjoerd H. van der Burg Ferry Ossendorp Cornelis J. M. Melief 《European journal of immunology》2013,43(10):2554-2565
The efficiency of antigen (Ag) processing by dendritic cells (DCs) is vital for the strength of the ensuing T‐cell responses. Previously, we and others have shown that in comparison to protein vaccines, vaccination with synthetic long peptides (SLPs) has shown more promising (pre‐)clinical results. Here, we studied the unknown mechanisms underlying the observed vaccine efficacy of SLPs. We report an in vitro processing analysis of SLPs for MHC class I and class II presentation by murine DCs and human monocyte‐derived DCs. Compared to protein, SLPs were rapidly and much more efficiently processed by DCs, resulting in an increased presentation to CD4+ and CD8+ T cells. The mechanism of access to MHC class I loading appeared to differ between the two forms of Ag. Whereas whole soluble protein Ag ended up largely in endolysosomes, SLPs were detected very rapidly outside the endolysosomes after internalization by DCs, followed by proteasome‐ and transporter associated with Ag processing‐dependent MHC class I presentation. Compared to the slower processing route taken by whole protein Ags, our results indicate that the efficient internalization of SLPs, accomplished by DCs but not by B or T cells and characterized by a different and faster intracellular routing, leads to enhanced CD8+ T‐cell activation. 相似文献
998.
Mark William Lopes Flávia Mahatma Schneider Soares Nelson de Mello Jean Costa Nunes Aurilene Gomes Cajado Daniel de Brito Fabiano Mendes de Cordova Rodrigo Maranguape Silva da Cunha Roger Walz Rodrigo Bainy Leal 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2013,226(2):153-163
The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. It has been demonstrated in this model that the phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit is increased 1 h after pilocarpine treatment. Moreover, alterations in the levels of glutamate transporters have been associated with chronic epilepsy in humans. Despite these studies, the profile of these changes has not yet been addressed. We analyzed the protein content and phosphorylation profile of the AMPA receptor GluR1 subunit by western blotting. We also used quantitative real-time polymerase chain reaction to analyze the expression of glial glutamate transporters and the N-methyl-d-aspartate receptor NR1 subunit in the hippocampus (Hip) and cerebral cortex (Ctx) at different time points after pilocarpine-induced status epilepticus (Pilo-SE) in male adult Wistar rats. Biochemical analysis was performed in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period), and 50 days (chronic period) after Pilo-SE. Key findings include an increase in the phosphorylation of GluR1-Ser845 in the Ctx and GluR1-Ser831 in the Hip at different times during the acute period, and a decrease in the total content of the GluR1 subunit in the Ctx in the latent period. There was a down-regulation of the mRNA expression and protein levels of EAAT1 and EAAT2, and a decrease of the NR1 mRNA expression, in the Ctx during the latent period. Notably, during the chronic period, the EAAT2 mRNA expression and protein levels decreased while the NR1 mRNA levels increased in the Hip. Taken together, our findings suggest a time- and structure-dependent imbalance of glutamatergic transmission in response to Pilo-SE, which might be associated with either epileptogenesis or the seizure threshold in MTLE-HS. 相似文献
999.
Renata Longhini Priscila Aparecida de Oliveira Ana Paula de Souza Faloni Estela Sasso‐Cerri Paulo Sérgio Cerri 《Journal of anatomy》2013,222(2):239-247
It has been demonstrated that histamine interferes with the recruitment, formation and activity of osteoclasts via H1‐ and H2‐receptors. Cimetidine is a H2‐receptor antagonist used for treatment of gastric ulcers that seems to prevent bone resorption. In this study, a possible cimetidine interference was investigated in the number of alveolar bone osteoclasts. The incidence of osteoclast apoptosis and immunoexpression of RANKL (receptor activator of nuclear factor κB ligand) was also evaluated. Adult male rats were treated with 100 mg kg?1 of cimetidine for 50 days (CimG); the sham group (SG) received saline. Maxillary fragments containing the first molars and alveolar bone were fixed, decalcified and embedded in paraffin. The sections were stained by H&E or submitted to tartrate‐resistant acid phosphatase (TRAP) method. TUNEL (terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling) method and immunohistochemical reactions for detecting caspase‐3 and RANKL were performed. The number of TRAP‐positive osteoclasts, the frequency of apoptotic osteoclasts and the numerical density of RANKL‐positive cells were obtained. Osteoclast death by apoptosis was confirmed by transmission electron microscopy (TEM). In CimG, TRAP‐positive osteoclasts with TUNEL‐positive nuclei and caspase‐3‐immunolabeled osteoclasts were found. A significant reduction in the number of TRAP‐positive osteoclasts and a high frequency of apoptotic osteoclasts were observed in CimG. Under TEM, detached osteoclasts from the bone surface showed typical features of apoptosis. Moreover, a significant reduction in the numerical density of RANKL‐positive cells was observed in CimG. The significant reduction in the number of osteoclasts may be due to cimetidine‐induced osteoclast apoptosis. However, RANKL immunoexpression reduction also suggests a possible interference of cimetidine treatment in the osteoclastogenesis. 相似文献
1000.