全文获取类型
收费全文 | 7768篇 |
免费 | 491篇 |
国内免费 | 27篇 |
专业分类
耳鼻咽喉 | 83篇 |
儿科学 | 236篇 |
妇产科学 | 243篇 |
基础医学 | 1266篇 |
口腔科学 | 235篇 |
临床医学 | 768篇 |
内科学 | 1693篇 |
皮肤病学 | 191篇 |
神经病学 | 710篇 |
特种医学 | 154篇 |
外科学 | 688篇 |
综合类 | 51篇 |
一般理论 | 5篇 |
预防医学 | 709篇 |
眼科学 | 120篇 |
药学 | 540篇 |
中国医学 | 12篇 |
肿瘤学 | 582篇 |
出版年
2024年 | 7篇 |
2023年 | 60篇 |
2022年 | 127篇 |
2021年 | 296篇 |
2020年 | 171篇 |
2019年 | 236篇 |
2018年 | 259篇 |
2017年 | 210篇 |
2016年 | 231篇 |
2015年 | 242篇 |
2014年 | 278篇 |
2013年 | 409篇 |
2012年 | 664篇 |
2011年 | 618篇 |
2010年 | 354篇 |
2009年 | 300篇 |
2008年 | 543篇 |
2007年 | 550篇 |
2006年 | 496篇 |
2005年 | 538篇 |
2004年 | 410篇 |
2003年 | 385篇 |
2002年 | 331篇 |
2001年 | 41篇 |
2000年 | 34篇 |
1999年 | 56篇 |
1998年 | 51篇 |
1997年 | 45篇 |
1996年 | 45篇 |
1995年 | 43篇 |
1994年 | 30篇 |
1993年 | 34篇 |
1992年 | 24篇 |
1991年 | 25篇 |
1990年 | 13篇 |
1989年 | 13篇 |
1988年 | 10篇 |
1987年 | 8篇 |
1986年 | 8篇 |
1985年 | 14篇 |
1984年 | 9篇 |
1983年 | 9篇 |
1982年 | 7篇 |
1981年 | 4篇 |
1980年 | 9篇 |
1978年 | 3篇 |
1972年 | 3篇 |
1970年 | 6篇 |
1968年 | 3篇 |
1965年 | 4篇 |
排序方式: 共有8286条查询结果,搜索用时 15 毫秒
151.
Low circulating IGF-I levels in hyperthyroidism are associated with decreased GH response to GH-releasing hormone 总被引:1,自引:0,他引:1
João C. Ramos-Dias Martin Yateman† Cecilia Camacho-Hübner† Ashley Grossman‡ Ana-Marla J. Lengyel 《Clinical endocrinology》1995,43(5):583-589
OBJECTIVE Several abnormalities In the GH response to pharmacological stimuli have been described in hyperthyroidism. Both normal and high serum IGF-I levels have been reported, as well as a decrease in IGF-I bioactivity. We have evaluated the GH response to GH-releasing hormone (GHRH) in hyperthyroid patients and the effects of hyperthyroidism on serum IGF-I levels. The possible relations between nutritional status, thyroid hormones and IGF-I levels were also investigated. We also studied the influence of long-term β-adrenoceptor blockade on the GH response to GHRH In these patients. DESIGN In 18 hyperthyroid patients and In 12 control subjects, GHRH (100μg) was administered as an i.v. bolus injection. Eight hyperthyroid patients and 8 control subjects received 50 μg GHRH i.v. Seven hyperthyroid patients were reevaluated after β-adrenoceptor blockade. IGF-I and albumin levels were measured Initially in all hyperthyroid patients and control subjects. Body composition was determined in 11 hyperthyroid patients and in a group of 33 matched normal controls. PATIENTS Hyperthyroid patients were compared to control subjects. MEASUREMENTS GH, TSH and free 14 were measured by Immunofluorometric assay. IGF-I, total T3 and total T4 were measured by radioimmunoassay. Body composition was determined using a dual-energy X-ray absorptfometer. RESULTS The GH response to 100 μg GHRH in hyper thyroid patients was blunted compared to control subjects. The mean peak GH levels and the area under the curve were significantly lower in hyperthyroid patients compared to control subjects (11 ± 1 vs 27 ± 5 μg/l and 820 ± 113 vs 1879 ± 355 μg/l 120 min, respectively; P <0.01). IGF-I levels were significantly reduced in hyperthyroid patients compared to controls (131 ± 10 vs 201 ± 16 μg/l, respectively; P <0.01). Ideal body weight, serum albumin levels and the lean body mass were also reduced In hyperthyroid patients. After β-adrenoceptor blockade there were no changes in the blunted GH response to GHRH in hyperthyroid patients. CONCLUSION Our data suggest that the blunted GH response to GHRH In hyperthyroidism is apparently not related to circulating IGF-I levels. It is possible that nutritional factors could play a role in the reduced circulating IGF-I levels found In these patients. 相似文献
152.
Glucagon induces the plasma membrane insertion of functional aquaporin-8 water channels in isolated rat hepatocytes 总被引:14,自引:0,他引:14
Gradilone SA García F Huebert RC Tietz PS Larocca MC Kierbel A Carreras FI Larusso NF Marinelli RA 《Hepatology (Baltimore, Md.)》2003,37(6):1435-1441
Although glucagon is known to stimulate the cyclic adenosine monophosphate (cAMP)-mediated hepatocyte bile secretion, the precise mechanisms accounting for this choleretic effect are unknown. We recently reported that hepatocytes express the water channel aquaporin-8 (AQP8), which is located primarily in intracellular vesicles, and its relocalization to plasma membranes can be induced with dibutyryl cAMP. In this study, we tested the hypothesis that glucagon induces the trafficking of AQP8 to the hepatocyte plasma membrane and thus increases membrane water permeability. Immunoblotting analysis in subcellular fractions from isolated rat hepatocytes indicated that glucagon caused a significant, dose-dependent increase in the amount of AQP8 in plasma membranes (e.g., 102% with 1 micromol/L glucagon) and a simultaneous decrease in intracellular membranes (e.g., 38% with 1 micromol/L glucagon). Confocal immunofluorescence microscopy in cultured hepatocytes confirmed the glucagon-induced redistribution of AQP8 from intracellular vesicles to plasma membrane. Polarized hepatocyte couplets showed that this redistribution was specifically to the canalicular domain. Glucagon also significantly increased hepatocyte membrane water permeability by about 70%, which was inhibited by the water channel blocker dimethyl sulfoxide (DMSO). The inhibitors of protein kinase A, H-89, and PKI, as well as the microtubule blocker colchicine, prevented the glucagon effect on both AQP8 redistribution to hepatocyte surface and cell membrane water permeability. In conclusion, our data suggest that glucagon induces the protein kinase A and microtubule-dependent translocation of AQP8 water channels to the hepatocyte canalicular plasma membrane, which in turn leads to an increase in membrane water permeability. These findings provide evidence supporting the molecular mechanisms of glucagon-induced hepatocyte bile secretion. 相似文献
153.
154.
Piero Barbanti MD PhD Luisa Fofi MD Licia Grazzi MD Fabrizio Vernieri MD Cecilia Camarda MD Paola Torelli MD Sabina Cevoli MD PhD Antonio Russo MD PhD Francesco Bono MD Cinzia Finocchi MD Renata Rao MD Stefano Messina MD Roberto De Simone MD Nicola Vanacore MD PhD Stefano Bonassi PhD ERT IRON Study Group 《Headache》2021,61(6):936-950
155.
Catherine Riou Elsa du Bruyn Cari Stek Remy Daroowala Rene T. Goliath Fatima Abrahams Qonita Said-Hartley Brian W. Allwood Nei-Yuan Hsiao Katalin A. Wilkinson Cecilia S. Lindestam Arlehamn Alessandro Sette Sean Wasserman Robert J. Wilkinson 《The Journal of clinical investigation》2021,131(12)
T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2–specific (SARS-CoV-2–specific) CD4+ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non–COVID-19 patients. We showed that SARS-CoV-2–specific CD4+ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1–mediated CD4+ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS-CoV-2–specific CD4+ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis–specific CD4+ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2–specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease. 相似文献
156.
Human leukocyte antigen (HLA) class I alleles are known to affect the cytotoxic T lymphocyte responses and influence susceptibility to viral infections. The objective of the present study was to find out whether HLA class I alleles are associated with clinical manifestations of dengue virus infection. The profile of HLA class I alleles were investigated in 224 human subjects [85 dengue fever (DF) cases, 29 dengue hemorrhagic fever (DHF) cases and 110 healthy controls (HCs)] from Western India using PCR based methods. Results revealed significantly higher frequency of HLA-A∗33 in DF cases compared to HCs [P = 0.032, Odds ratio (OR) 2.12]. The frequency of HLA-A∗02:11 was higher in DHF cases compared to DF cases. The frequency of HLA-B∗18 was significantly higher in dengue (DEN) cases [P = 0.047 Pc = 0.846, OR 3.53]. The frequency of HLA-Cw∗07 allele was significantly higher in DEN cases [DEN vs. HCs: P = 0.0120, Pc = 0.168, OR 2.00]. Significance was observed even when the cases were categorized in to DF and DHF [DF vs. HCs: P = 0.0349, Pc = 0.49, OR 1.87; DHF vs. HCs: P = 0.0399, Pc = 0.56, OR 2.4]. The combined frequency of HLA-Cw∗07 with HLA-DRB1∗07/∗15 genotype was significantly higher in DHF cases as compared to DF and HCs [DHF vs. HCs: P = 0.022, OR 5.31; DHF vs. DF: P = 0.027, OR 5.49]. On the other hand, the frequency of combination of HLA-Cw∗07 without HLA-DRB1∗07 was significantly higher in DF cases compared to HCs [DF vs. HCs: P = 0.002, OR 2.42 (1.28–4.55)]. The results suggest that HLA-A∗∗33 may be associated with DF while HLA-B∗18 and HLA-Cw∗07 alleles may be associated with symptomatic dengue requiring hospitalization. In the presence of HLA-DRB1∗07/∗15 genotype, HLA-Cw∗07 is associated with increased risk of developing DHF while in the presence of other HLA-DRB1 alleles, HLA-Cw∗07 is associated with DF. 相似文献
157.
Luca Passamonti Francesco Fera Alessandro Tessitore Antonio Russo Antonio Cerasa Cecilia M. Gioia Maria R. Monsurrò Raffaella Migliaccio Gioacchino Tedeschi Aldo Quattrone 《Neurobiology of aging》2013
Previous studies have shown that affective symptoms are part of the clinical picture in amyotrophic lateral sclerosis (ALS), the most common motor neuron disorder in elderly people. Diffuse neurodegeneration of limbic regions (e.g., prefrontal cortex [PFC], amygdala) was demonstrated in ALS post-mortem, although the mechanisms of emotional dysregulation in ALS in vivo remain unclear. Using functional imaging, we assessed the brain responses to emotional faces in 11 cognitively unimpaired ALS patients and 12 healthy controls (HCs). We tested whether regional activities and connectivity patterns in the limbic system differed between ALS patients and HCs and whether the variability in clinical measures modulated the neuroimaging data. Relative to HCs, ALS patients displayed greater activation in a series of PFC areas and altered left amygdala–PFC connectivity. Anxiety modulated the right amygdala–PFC connectivity in HCs but not in ALS patients. Reduced right premotor cortex activity and altered left amygdala–supplementary motor area connectivity were associated with longer disease duration and greater disease severity, respectively. Our findings demonstrate dysfunctions of the limbic system in ALS patients at early stages of the disease, and extend our knowledge about the interplay between emotional brain areas and the regions traditionally implicated in motor control. 相似文献
158.
159.
Roberto Ronca Patrizia Alessi Daniela Coltrini Emanuela Di Salle Arianna Giacomini Daria Leali Michela Corsini Mirella Belleri Chiara Tobia Cecilia Garlanda Elisa Bonomi Regina Tardanico William Vermi Marco Presta 《The Journal of pathology》2013,230(2):228-238
Fibroblast growth factors (FGFs) exert autocrine/paracrine functions in prostate cancer by stimulating angiogenesis and tumour growth. Here dihydrotestosterone (DHT) up‐regulates FGF2 and FGF8b production in murine TRAMP‐C2 prostate cancer cells, activating a FGF‐dependent autocrine loop of stimulation. The soluble pattern recognition receptor long pentraxin‐3 (PTX3) acts as a natural FGF antagonist that binds FGF2 and FGF8b via its N‐terminal domain. We demonstrate that recombinant PTX3 protein and the PTX3‐derived pentapeptide Ac‐ARPCA‐NH2 abolish the mitogenic response of murine TRAMP‐C2 cells and human LNCaP prostate cancer cells to DHT and FGFs. Also, PTX3 hampers the angiogenic activity of DHT‐activated TRAMP‐C2 cells on the chick embryo chorioallantoic membrane (CAM). Accordingly, human PTX3 overexpression inhibits the mitogenic activity exerted by DHT or FGFs on hPTX3_TRAMP‐C2 cell transfectants and their angiogenic activity. Also, hPTX3_TRAMP‐C2 cells show a dramatic decrease of their angiogenic and tumourigenic potential when grafted in syngeneic or immunodeficient athymic male mice. A similar inhibitory effect is observed when TRAMP‐C2 cells overexpress only the FGF‐binding N‐terminal PTX3 domain. In keeping with the anti‐tumour activity of PTX3 in experimental prostate cancer, immunohistochemical analysis of prostate needle biopsies from primary prostate adenocarcinoma patients shows that parenchymal PTX3 expression, abundant in basal cells of normal glands, is lost in high‐grade prostatic intraepithelial neoplasia and in invasive tumour areas. These results identify PTX3 as a potent FGF antagonist endowed with anti‐angiogenic and anti‐neoplastic activity in prostate cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
160.
Mara Cerqueiro Bybrant Lena Grahnquist Eva Örtqvist Cecilia Andersson Gun Forsander Helena Elding Larsson 《Autoimmunity》2013,46(5):221-227
AbstractObjectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18?years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p?=?.00001) and those with DQX/X (p?≤?.00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p?=?.018).Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD. 相似文献