全文获取类型
收费全文 | 30058篇 |
免费 | 1775篇 |
国内免费 | 182篇 |
专业分类
耳鼻咽喉 | 198篇 |
儿科学 | 909篇 |
妇产科学 | 603篇 |
基础医学 | 4499篇 |
口腔科学 | 550篇 |
临床医学 | 2418篇 |
内科学 | 7553篇 |
皮肤病学 | 496篇 |
神经病学 | 3057篇 |
特种医学 | 1103篇 |
外科学 | 2930篇 |
综合类 | 78篇 |
一般理论 | 6篇 |
预防医学 | 1948篇 |
眼科学 | 314篇 |
药学 | 2177篇 |
中国医学 | 74篇 |
肿瘤学 | 3102篇 |
出版年
2023年 | 243篇 |
2022年 | 498篇 |
2021年 | 893篇 |
2020年 | 532篇 |
2019年 | 740篇 |
2018年 | 816篇 |
2017年 | 671篇 |
2016年 | 760篇 |
2015年 | 819篇 |
2014年 | 1100篇 |
2013年 | 1451篇 |
2012年 | 2258篇 |
2011年 | 2334篇 |
2010年 | 1280篇 |
2009年 | 1161篇 |
2008年 | 1907篇 |
2007年 | 1855篇 |
2006年 | 1714篇 |
2005年 | 1541篇 |
2004年 | 1411篇 |
2003年 | 1245篇 |
2002年 | 1128篇 |
2001年 | 481篇 |
2000年 | 457篇 |
1999年 | 512篇 |
1998年 | 264篇 |
1997年 | 204篇 |
1996年 | 200篇 |
1995年 | 134篇 |
1994年 | 126篇 |
1993年 | 128篇 |
1992年 | 301篇 |
1991年 | 284篇 |
1990年 | 288篇 |
1989年 | 258篇 |
1988年 | 200篇 |
1987年 | 180篇 |
1986年 | 193篇 |
1985年 | 214篇 |
1984年 | 136篇 |
1983年 | 108篇 |
1982年 | 79篇 |
1981年 | 57篇 |
1980年 | 52篇 |
1979年 | 113篇 |
1977年 | 60篇 |
1976年 | 57篇 |
1975年 | 58篇 |
1973年 | 66篇 |
1971年 | 51篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
121.
Patrizia Robino Ilario Ferrocino Giacomo Rossi Andrea Dogliero Valentina Alessandria Lisa Grosso 《Avian pathology》2019,48(2):111-120
Macrorhabdus ornithogaster is an opportunistic yeast that colonizes the gastric mucosa of many avian species. Until now, no studies have focused on the influence of a gastric infection on the balance of the intestinal microbiota of birds. In this study, 44 faecal samples from individual canaries, with and without M. ornithogaster infection, were analysed. The detection of the yeast was evaluated by 18S rRNA PCR. In order to evaluate the impact of the Macrorhabdus infection on the bacterial communities, culture-independent methods, by the use of amplicon-based sequencing as well as 16S rRNA-DGGE, were adopted. The different health status of animals affected the relative abundance of the main OTUs, with a greater diversification of the gut microbiota in healthy animals compared to the infected. In particular, Lactococcus, Pseudomonas, Acinetobacter, Lachnospiraceae, Propionibacterium and Weissella were found to be characteristic of uninfected animals (FDR?<?0.05), while Lactobacillus and Candidatus Arthromitus were characteristic of infected animals (FDR?<?0.05). Both these taxa have been reported as immunostimulatory, involved in immunological disorders. In infected animals the inferred metagenome assessed by PICRUST clearly showed a positive correlation between the presence of M. ornithogaster and KEGG genes related to ether lipid metabolism, already reported to be immunostimulatory by activation of macrophages and to play a pathophysiological role in several immunological disorders. Finally, our results show an interaction between infection of the digestive tract and intestinal microbiota of pet birds and provide insight into the changing of the complex enteric bacterial community.
- HIGHLIGHTS
Macrorabdus ornithogaster is a gastric yeast that colonizes a wide range of birds.
Differences were found between infected and healthy animals in gut microbiota.
Candidatus Arthromitus was closely associated with infected birds.
M. ornithogaster can affect intestinal microbiota composition of canaries.
122.
Spectral karyotyping of prostate cell lines LNCaP, DU145, PC3, and 22RV demonstrated structural chromosome rearrangements involving the distal long arm of chromosome 4. In all but 22RV, these are nonreciprocal translocations between chromosomes 4 and 10. In 22RV, an apparently reciprocal t(2q;4q) is seen. Fluorescence in situ hybridization analysis of the chromosome 4 translocation breakpoints demonstrated that deletions were associated with all of the translocations, resulting in a net loss of chromosome material. Overlapping deletions in 4q28 approximately 34 were seen in LNCap, DU145, and 22RV, which defined an approximately 4.5-megabase pair common region of deletion. The deletion in PC3 was more proximal on 4q, involving the 4q21 approximately q26 region. A meta analysis of high-resolution definition of losses of chromosome material from published studies demonstrates that loss of 4q material may occur in at least 50% of primary tumors. This analysis defines a series of genes in the critical 4q region, which is potentially associated with prostate tumor development. 相似文献
123.
Palermo B Garbelli S Mantovani S Scoccia E Da Prada GA Bernabei P Avanzini MA Brazzelli V Borroni G Giachino C 《European journal of immunology》2005,35(11):3153-3162
Vitiligo is a skin disorder characterized by depigmented macules secondary to melanocyte loss. An unusual facet is its relation to melanoma: cytotoxic T lymphocytes directed to melanocyte antigens are found in both conditions and imply a breakdown of tolerance, yet the resulting immune reaction is the opposite. The mechanisms at the basis of these opposite effects are not known. Here, we performed a direct comparison of whole melanocyte-specific T cell populations in the two diseases. We demonstrate that neither precursor frequencies of Melan-A/MART-1-specific T lymphocytes nor their status of activation differ significantly. However, by using a tetramer-based T cell receptor down-regulation assay, we documented a higher affinity of vitiligo T cells. We calculated that the peptide concentration required for 50% of maximal receptor down-regulation differed by 6.5-fold between the two diseases. Moreover, only vitiligo T cells were capable of efficient receptor down-regulation and IFN-gamma production in response to HLA-matched melanoma cells, suggesting that this difference in receptor affinity is physiologically relevant. The differences in receptor affinity and tumor reactivity were confirmed by analyzing Melan-A/MART-1-specific clones established from the two diseases. Our results suggest that the quality, and not the quantity, of the melanocyte-specific cytotoxic responses differs between the two pathologies. 相似文献
124.
Chini L Bardare M Cancrini C Angelini F Mancia L Cortis E Finocchi A Riccardi C Rossi P 《Scandinavian journal of immunology》2002,56(5):512-517
Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are characterized by chronic inflammation, synovial cell proliferation and progressive joint damage. It has been speculated that T cells play an important role in the pathogenesis of RA and JRA in the early stage of the disease. Previous studies have demonstrated discrepant results regarding the significance of T-cell clonality in RA or JRA lesions. It can be postulated that the heterogeneity of these data may be linked to the stage of the disease, as the relative importance of selective immunological events is different during the time from onset to established disease. To avoid this problem, we conducted the present study in nine children affected by JRA at the onset of the disease and before treatment. We analysed the T-cell receptor beta chain variable (TCRBV) of CD4+ and CD8+ lymphocytes in peripheral blood (PBL) and synovial fluid (SFL), by a panel of monoclonal antibodies (MoAbs). Furthermore, to assess the clonotypic pattern of T-cell repertoire, the CDR3 length distribution was evaluated by spectratyping analysis. Our results showed no significant expansion of distinct TCRBV subset in either synovial or peripheral compartments. Conversely, when we studied the CDR3 length distribution, an oligoclonal pattern was found in the SFL of six patients, suggesting the presence of a clonotypic restriction of T cells in SFL, which is not detectable in PBL. These findings are consistent with an antigen driven T-cell expansion sequestered at the inflammatory site. 相似文献
125.
Renate A. Morawetz G. Paolo Rizzardi Didier Glauser Olivier Rutschmann Bernard Hirschel Luc Perrin Milos Opravil Markus Flepp Jan von Overbeck Michel P. Glauser Silvia Ghezzi Elisa Vicenzi Guido Poli Adriano Lazzarin 《European journal of immunology》1997,27(12):3223-3227
Homozygous (Δccr5/Δccr5) and heterozygous (CCR5/Δccr5) deletions in the β-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/Δccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts >500/μl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/Δccr5 genotype. However, when LTNP were analyzed separetely, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69 % of LTNP) and the heterozygous (31.0 %) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/Δccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/Δccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease. 相似文献
126.
Evaluation of stromal metalloproteinases and vascular endothelial growth factors in a spontaneous metastasis model 总被引:5,自引:0,他引:5
Donadio AC Durand S Remedi MM Frede S Ceschin DG Genti-Raimondi S Chiabrando GA 《Experimental and molecular pathology》2005,79(3):259-264
This study aims to investigate MMP2 and MT1-MMP protein as well as VEGF-C and VEGF-D mRNA expression in tumor cells and distant organs considered to be targets for metastasis in a tumor spontaneous metastasis model previously described. Cultured tumor cells, able to express pro-MMP2, MMP2, pro-MMP9, and MT1-MMP, develop tumor growth and metastasis, mainly in the liver and spleen, when they are injected in the mammary pad gland of Wistar rats. Immunohistochemical studies of tumor masses showed small groups of tumor cells staining for MT1-MMP but not for MMP2. In the liver, tumor metastatic foci and a stromal positive staining for both MMP2 and MT1-MMP were shown. The spleen and lymph nodes, with only scattered metastatic cells, did not show MMPs immunostaining. Using RT-PCR, a significantly higher VEGF-C and VEGF-D gene expression was shown in the liver of tumor-bearing rats respect to normal rats, whereas spleen and lymph nodes did not show significant differences in mRNA VEGF-C/D levels. Taken together, our results suggest that the stroma microenvironment of target organs for metastasis has the ability to produce MMPs and VEGFs that facilitate the anchorage of tumor cells and promote tumor cell growth and angiogenesis. 相似文献
127.
128.
LPS resistance in monocytic cells caused by reverse signaling through transmembrane TNF (mTNF) is mediated by the MAPK/ERK pathway 总被引:1,自引:0,他引:1
Kirchner S Boldt S Kolch W Haffner S Kazak S Janosch P Holler E Andreesen R Eissner G 《Journal of leukocyte biology》2004,75(2):324-331
The transmembrane form of tumor necrosis factor (mTNF), expressed on activated monocytes (MO) and macrophages (MPhi), is able to induce apoptosis in human endothelial cells (EC). Apoptosis is mediated by two distinct mechanisms: direct cell contact and a yet-unidentified soluble protein, death factor X. In addition, mTNF acts as a receptor that transduces a "reverse signal" into MO/MPhi when bound to the TNF receptor on EC. Reverse signaling by mTNF confers resistance to bacterial lipopolysaccharide (LPS). Stimulation of reverse signaling by mTNF blocks the ability of MO/MPhi to produce death factor X and proinflammatory cytokines. We have investigated which signaling pathways are used by mTNF acting as receptor. Reverse signaling triggers two independent pathways that can be distinguished by protein kinase C (PKC) inhibitors. The suppression of LPS-induced death factor X is dependent on PKC, whereas the suppression of LPS-mediated cytokine release is not. LPS and reverse signaling stimulate the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. It is interesting that the activation of reverse signaling by mTNF renders MO/MPhi refractory to a subsequent activation of the MAPK/ERK pathway by LPS. Thus, reverse signaling achieves LPS resistance in monocytic cells through interference with key signal-transduction pathways. 相似文献
129.
Immunoglobulin E and eosinophil-dependent protective immunity to larval Onchocerca volvulus in mice immunized with irradiated larvae
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Abraham D Leon O Schnyder-Candrian S Wang CC Galioto AM Kerepesi LA Lee JJ Lustigman S 《Infection and immunity》2004,72(2):810-817
Mice immunized with irradiated Onchocerca volvulus third-stage larvae developed protective immunity. Eosinophil levels were elevated in the parasite microenvironment at the time of larval killing, and measurements of total serum antibody levels revealed an increase in the immunoglobulin E (IgE) level in immunized mice. The goal of the present study was to identify the role of granulocytes and antibodies in the protective immune response to the larval stages of O. volvulus in mice immunized with irradiated larvae. Immunity did not develop in mice if granulocytes, including both neutrophils and eosinophils, were eliminated, nor did it develop if only eosinophils were eliminated. Moreover, larvae were killed in na?ve interleukin-5 transgenic mice, and the killing coincided with an increase in the number of eosinophils and the eosinophil peroxidase (EPO) level in the animals. To determine if EPO was required for protective immunity, mice that were genetically deficient in EPO were immunized, and there were no differences in the rates of parasite recovery in EPO-deficient mice and wild-type mice. Two mouse strains were used to study B-cell function; micro MT mice lacked all mature B cells, and Xid mice had deficiencies in the B-1 cell population. Immunity did not develop in the micro MT mice but did develop in the Xid mice. Finally, protective immunity was abolished in mice treated to eliminate IgE from the blood. We therefore concluded that IgE and eosinophils are required for adaptive protective immunity to larval O. volvulus in mice. 相似文献
130.
Peripheral blood dendritic cells increase in kidney-transplant patients without rejection 总被引:2,自引:0,他引:2
Saresella M Marini M Guerini F Ferrante P Della Bella S Chiaramonte S Riva A 《Clinical immunology (Orlando, Fla.)》2004,110(2):191-3; author reply 194