全文获取类型
收费全文 | 1421篇 |
免费 | 108篇 |
国内免费 | 15篇 |
专业分类
耳鼻咽喉 | 7篇 |
儿科学 | 51篇 |
妇产科学 | 46篇 |
基础医学 | 199篇 |
口腔科学 | 33篇 |
临床医学 | 132篇 |
内科学 | 412篇 |
皮肤病学 | 20篇 |
神经病学 | 122篇 |
特种医学 | 18篇 |
外科学 | 134篇 |
综合类 | 3篇 |
预防医学 | 77篇 |
眼科学 | 19篇 |
药学 | 101篇 |
中国医学 | 4篇 |
肿瘤学 | 166篇 |
出版年
2024年 | 1篇 |
2023年 | 9篇 |
2022年 | 30篇 |
2021年 | 48篇 |
2020年 | 20篇 |
2019年 | 29篇 |
2018年 | 40篇 |
2017年 | 37篇 |
2016年 | 48篇 |
2015年 | 41篇 |
2014年 | 61篇 |
2013年 | 95篇 |
2012年 | 117篇 |
2011年 | 110篇 |
2010年 | 53篇 |
2009年 | 71篇 |
2008年 | 94篇 |
2007年 | 93篇 |
2006年 | 85篇 |
2005年 | 76篇 |
2004年 | 105篇 |
2003年 | 75篇 |
2002年 | 81篇 |
2001年 | 9篇 |
2000年 | 3篇 |
1999年 | 6篇 |
1998年 | 16篇 |
1997年 | 10篇 |
1996年 | 4篇 |
1995年 | 11篇 |
1994年 | 11篇 |
1993年 | 5篇 |
1992年 | 7篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 7篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1974年 | 2篇 |
1970年 | 1篇 |
排序方式: 共有1544条查询结果,搜索用时 0 毫秒
41.
Maglione V Cannella M Gradini R Cislaghi G Squitieri F 《Mechanisms of ageing and development》2006,127(2):213-216
Huntington's disease (HD) is caused by mutated huntingtin (htt), a toxic protein ubiquitously expressed in nervous and non-nervous system tissues. Fragmentation of htt by caspases and further accumulation in cells of protein aggregates contribute to cell dysfunction and death. In the attempt to elucidate whether this mechanism depends on patients' genotype, we analysed the pattern of htt fragmentation, the caspase 3, 8 and 9 activities and their variation in lymphoblasts with heterozygous and homozygous CAG mutation and in controls. Cells homozygous for expanded mutation showed greater amount of mutated fragments than heterozygotes and controls, caspase 3, 8 and 9 activities greater in mutated than control cell lines, after cyanide treatment, the caspase 3 and 8 particularly increased in homozygotes. This data offers a biological explanation to the clinical in-patients evidence of mutation homozygosity associated with more severe phenotype. 相似文献
42.
The presence and distribution patterns of ghrelin, a gastric acylated peptide, were studied in the entire gastrointestinal tract of the chicken (Gallus domesticus) using the peroxidase-antiperoxidase immunohistochemical method, western blot analysis and a specific antibody against the C-terminal region of rat ghrelin. Ghrelin-immunopositive cells were observed in the mucosal layer of all segments examined. The largest numbers of ghrelin-positive cells were located at the base of lobuli of the proventriculus gland, along villi of the intestines and in crypts of the duodenum. Lower numbers of ghrelin-immunostained cells were located in crypts of jejunum and ileum and only few ghrelin-immunostained cells were detected at the base of crypts of the large intestine. Closed and open types of cells were observed in all segments. Western blot analysis confirmed the presence of ghrelin-like protein in the entire chicken gastrointestinal tract. The anatomical distribution patterns and the morphological characteristics of chicken ghrelin-positive cells suggest that they are endocrine cells. Furthermore, it is concluded that ghrelin shows a high degree of preservation during evolution from non-mammalian vertebrates to mammals. 相似文献
43.
Francesco Leone Giuliana Cavalloni Monica Gunetti Ymera Pignochino Wanda Piacibello Massimo Aglietta 《Biology of blood and marrow transplantation》2006,12(1):68-74
Tumor cell contamination might induce relapse after autologous transplantation in breast cancer patients. We used an ex vivo purging strategy to decrease the number of contaminating breast tumor cells in leukaphereses without altering the engraftment potential of the hemopoietic progenitor cells. This method is based on immunoselection of CD34+ cells derived from mobilized peripheral blood of patients with metastatic breast cancer and expansion in the presence of flt3 ligand, stem cell factor, interleukin 6, and thrombopoietin. Tumor contamination before and after culture was monitored by mammaglobin messenger RNA amplification by quantitative polymerase chain reaction. We analyzed both adherent and suspended cells obtained after 2 weeks of culture. Hemopoietic progenitors were increased among suspended cells. In this fraction, tumor cell contamination was decreased, whereas it increased within the adherent cell fraction. Experimental models using CD34+ cells from healthy donors spiked with breast cancer cells were also constructed to investigate whether treatment with anti-ErbB-receptor drugs could further reduce the tumor load without affecting the clonogenic potential of hemopoietic cells. For this purpose, we successfully assayed trastuzumab, a monoclonal antibody against ErbB-2, and gefitinib, an epidermal growth factor receptor tyrosine kinase receptor inhibitor. These results suggest that positively selected CD34+ cells from cancer patients contain tumor cells and that ex vivo expansion can reduce the tumor load of the suspended fraction. Target-based agents against ErbB-2, epidermal growth factor receptor, or both--such as trastuzumab or gefitinib--might increase the efficiency of purging. 相似文献
44.
Sartori G Cavazza A Bertolini F Longo L Marchioni A Costantini M Barbieri F Migaldi M Rossi G 《American journal of clinical pathology》2008,129(2):202-210
Atypical adenomatous hyperplasia (AAH) is considered the preinvasive lesion of pulmonary adenocarcinoma, and mutations of EGFR, HER2, and K-ras are involved in the early stage of lung adenocarcinoma carcinogenesis, also predicting clinical response to anti-EGFR small molecule inhibitors. We analyzed 18 cases of primary lung adenocarcinoma with concomitant AAH foci from 13 patients for mutations of EGFR (exons 18-21), HER2 (exons 19-20), and K-ras (exon 2) by direct sequencing polymerase chain reaction. Among mutated cases, concordant mutations of EGFR or K-ras in adenocarcinoma and related AAH were observed in 5 (63%) of 8 cases. In particular, 3 of 4 adenocarcinomas with EGFR mutations (all L858R point mutations in women, never or former smokers) had a concomitant and identical mutation in AAH, and 2 of 4 adenocarcinomas with K-ras mutations (both at codon 12 in women, a never and a current smoker) showed the same mutation in concomitant AAH. All cases were wild-type for HER2. Mutations of EGFR and K-ras genes represent an early event in lung adenocarcinomagenesis, and AAH convincingly seems to be a precursor lesion in a subset of cases of adenocarcinoma. 相似文献
45.
Caterina Maria Gambino Danilo Di Bona Anna Aiello Ciriaco Carru Giovanni Duro Giuliana Guggino Angelo Ferrante Angelo Zinellu Calogero Caruso Giuseppina Candore Giulia Accardi 《Human immunology》2018,79(3):172-177
Recently, the role of killer cell immunoglobulin-like receptor (KIR) in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of KIR genes and the human leukocytes antigen (HLA) ligands with Systemic Lupus Erythematosus (SLE) and accompanying oxidative stress. Presence or absence of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method by case-control study. A total of 45 SLE patients, and 60 healthy controls, all of Sicilian descent, were enrolled. Plasma values of the anti-oxidant molecule Taurine were determined in all subjects by capillary electrophoresis UV detection. The carrier frequency of the KIR2DS2 gene was significantly increased in SLE patients compared to healthy controls (73.3 versus 45.0%; OR?=?3.36; 95% CI?=?1.46–7.74; p?=?.005) suggesting a role of KIR2DS2 gene in the susceptibility to disease. We also observed a strong positive association between the presence of HLA-C1 ligands group and the disease (82.2% in SLE patients versus 41.7% in controls; OR?=?6.47, 95% CI?=?2.58–16.26; p?<?.0001). Stepwise logistic regression analysis supported the effect of the HLA-C1 ligands in SLE patients (OR?=?7.06, 95% CI?=?0.07–2.19; p?=?.002), while the KIR genes were no longer significant. Interestingly, we found that SLE patients HLA-C1 positive showed significantly decreased plasma levels of antioxidant activity marker Taurine (69.38?±?28.49?μmol/L) compared to SLE patients HLA-C1 negative (108.37?±?86.09?μmol/L) (p?=?.03). In conclusion, HLA-C1 ligands group was significantly associated with an increased risk of SLE as well as an increased oxidative stress status overall in SLE patients. 相似文献
46.
L. Reggiani Bonetti P. Ferrari N. Trani L. Maccio Schirosi Laura Sartori Giuliana F. Facchinetti F. Rivasi 《Archives of gynecology and obstetrics》2011,283(2):231-241
Purpose
To investigate the most plausible cause of stillbirth by evaluating clinical records and postmortem examination findings including placental analysis. 相似文献47.
Identification of a Promiscuous T-Cell Epitope in Mycobacterium tuberculosis Mce Proteins 总被引:4,自引:0,他引:4 下载免费PDF全文
Maddalena Panigada Tiziana Sturniolo Giorgio Besozzi Maria Giovanna Boccieri Francesco Sinigaglia Giuliana Gialdroni Grassi Fabio Grassi 《Infection and immunity》2002,70(1):79-85
The characterization of Mycobacterium tuberculosis antigens inducing CD4(+) T-cell responses could critically contribute to the development of subunit vaccines for M. tuberculosis. Here we performed computational analysis by using T-cell epitope prediction software (known as TEPITOPE) to predict promiscuous HLA-DR ligands in the products of the mce genes of M. tuberculosis. The analysis of the proliferative responses of CD4(+) T cells from patients with pulmonary tuberculosis to selected peptides displaying promiscuous binding to HLA-DR in vitro led us to the identification of a peptide that induced proliferation of CD4(+) cells from 50% of the tested subjects. This study demonstrates that a systematic computational approach can be used to identify T-cell epitopes in proteins expressed by an intracellular pathogen. 相似文献
48.
Losana G Bovolenta C Rigamonti L Borghi I Altare F Jouanguy E Forni G Casanova JL Sherry B Mengozzi M Trinchieri G Poli G Gerosa F Novelli F 《Journal of leukocyte biology》2002,72(4):735-742
Interleukin (IL)-12, especially in the presence of neutralizing anti-IL-4 monoclonal antibodies, primed CD45RO(-) T clones for high CCL3/macrophage-inflammatory protein-1alpha (MIP-1alpha) and CCL4/MIP-1beta levels. In CD4(+) and CD8(+) clones from two patients deficient for IL-12Rbeta1 (IL-12Rbeta1(-/-)), production of CCL3/MIP-1alpha and CCL4/MIP-1beta was defective. CD4(+) clones from two patients deficient for interferon-gamma (IFN-gamma) R1 (IFN-gammaR1(-/-)) produced somewhat decreased CCL4/MIP-1beta levels. IL-12 failed to prime CD4(+) or CD8(+) healthy clones for high CCL5/regulated on activation, normal T expressed and secreted (RANTES) production, although its secretion was impaired in CD4(+) clones from IL-12Rbeta1(-/-) and IFN-gammaR1(-/-) patients. CCR5 surface expression was up-regulated in resting peripheral blood mononuclear cells and CD4(+) clones from both kinds of patients, rendering them more susceptible to CCR5-dependent (R5) HIV-1 infection. Neutralization of IFN-gamma increased CCR5 expression and decreased CC-chemokine secretion by CD4(+) clones from healthy and IL-12Rbeta1(-/-) individuals, suggesting an IFN-gamma-dependent control of CCR5 expression. These data provide the first documented analysis of chemokine secretion and chemokine receptor expression on T cells from IL-12 and IFN-gamma receptor-deficient patients and dissect the role of IL-12 and IFN-gamma on inducing inflammatory chemokine secretion and down-regulating CCR5 expression in human T cells. 相似文献
49.
Wollmer MA Papassotiropoulos A Streffer JR Grimaldi LM Kapaki E Salani G Paraskevas GP Maddalena A de Quervain D Bieber C Umbricht D Lemke U Bosshardt S Degonda N Henke K Hegi T Jung HH Pasch T Hock C Nitsch RM 《Psychiatric genetics》2002,12(3):155-160
Tissue inhibitor of metalloproteinases 1 (TIMP-1) inhibits several proteinases including a disintegrin and metalloproteinase 10 (ADAM10), a major alpha-secretase that cleaves the beta-amyloid precursor protein within its amyloidogenic Abeta domain. The gene encoding TIMP-1 (TIMP 1) maps to the short arm of the X chromosome, in a region previously suggested as conferring genetic susceptibility for Alzheimer's disease (AD). To determine whether genetic variability of TIMP 1 contributes to the pathogenesis of AD, we analysed one single nucleotide polymorphism within TIMP 1 and one single nucleotide polymorphism in the 5'-untranslated region of TIMP 1 in patients with AD and control subjects from two independent and ethnically different populations. We did not observe any association between TIMP 1 genotypes and the diagnosis of AD in men or women. We also measured TIMP-1 protein levels in the cerebrospinal fluid of patients with AD, healthy control subjects, and patients with other neurological disorders. TIMP-1 levels were similar in all groups. In addition, no significant differences were observed after stratification for TIMP 1 genotypes. Our data show that neither genetic variability nor protein levels of TIMP-1 are associated with AD. 相似文献
50.
Chronic lymphocytic leukemia B cells are endowed with the capacity to attract CD4+, CD40L+ T cells by producing CCL22 总被引:6,自引:0,他引:6