全文获取类型
收费全文 | 353篇 |
免费 | 19篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 2篇 |
妇产科学 | 6篇 |
基础医学 | 47篇 |
口腔科学 | 6篇 |
临床医学 | 23篇 |
内科学 | 88篇 |
皮肤病学 | 3篇 |
神经病学 | 41篇 |
特种医学 | 10篇 |
外科学 | 21篇 |
综合类 | 1篇 |
一般理论 | 2篇 |
预防医学 | 30篇 |
眼科学 | 18篇 |
药学 | 37篇 |
肿瘤学 | 35篇 |
出版年
2024年 | 3篇 |
2023年 | 10篇 |
2022年 | 6篇 |
2021年 | 17篇 |
2020年 | 6篇 |
2019年 | 17篇 |
2018年 | 8篇 |
2017年 | 12篇 |
2016年 | 13篇 |
2015年 | 15篇 |
2014年 | 21篇 |
2013年 | 16篇 |
2012年 | 41篇 |
2011年 | 38篇 |
2010年 | 12篇 |
2009年 | 7篇 |
2008年 | 17篇 |
2007年 | 22篇 |
2006年 | 15篇 |
2005年 | 30篇 |
2004年 | 20篇 |
2003年 | 7篇 |
2002年 | 9篇 |
2000年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1991年 | 2篇 |
排序方式: 共有372条查询结果,搜索用时 0 毫秒
1.
Marius Schwabenland Henrike Salié Jovan Tanevski Saskia Killmer Marilyn Salvat Lago Alexandra Emilia Schlaak Lena Mayer Jakob Matschke Klaus Püschel Antonia Fitzek Benjamin Ondruschka Henrik E. Mei Tobias Boettler Christoph Neumann-Haefelin Maike Hofmann Angele Breithaupt Nafiye Genc Christine Stadelmann Bertram Bengsch 《Immunity》2021,54(7):1594-1610.e11
2.
Haufe S Engeli S Kast P Böhnke J Utz W Haas V Hermsdorf M Mähler A Wiesner S Birkenfeld AL Sell H Otto C Mehling H Luft FC Eckel J Schulz-Menger J Boschmann M Jordan J 《Hepatology (Baltimore, Md.)》2011,53(5):1504-1514
Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease. Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids. We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard. A total of 170 overweight and obese, otherwise healthy subjects were randomized to either reduced carbohydrate (n = 84) or reduced fat (n = 86), total energy restricted diet (-30% of energy intake before diet) for 6 months. Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography. Subjects were also submitted to fat spectroscopy of liver and oral glucose tolerance testing. In all, 102 subjects completed the diet intervention with measurements of intrahepatic lipid content. Both hypocaloric diets decreased body weight, total body fat, visceral fat, and intrahepatic lipid content. Subjects with high baseline intrahepatic lipids (>5.56%) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values (<5.56%) irrespective of diet composition. In contrast, changes in visceral fat mass and insulin sensitivity were similar between subgroups, with low and high baseline intrahepatic lipids. CONCLUSION: A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet. The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet. 相似文献
3.
Interleukin (IL)-10 down-regulates HLA class II molecules, whether constitutively expressed or up-regulated by interferon-γ or IL-4 on monocytes but not on B lymphocytes. In this study we show that IL-10 does not inhibit HLA class II expression induced by the combination granulocyte/macrophage colony-stimulating factor and IL-4 on monocytes, although it simultaneously abrogates the expression of CD1 molecules induced by the same combination of cytokines. CD1 molecules can act as element of genetic restriction for CD4? CD8? T lymphocytes, and the suppression of CD1 expression by IL-10 abolished antigen presentation to CD1-restricted CD4? CD8? T cell receptor-positive T cells. Although HLA class II expression was not down-regulated by IL-10, the antigen specific proliferative response of CD4+ T cells was nevertheless decreased. This was not caused by down-regulation of known co-stimulatory molecules such as B7.1, B7.2 and ICAM-1. IL-10 decreased the antigen specific proliferative response further by directly influencing the T lymphocytes. Our results indicate that IL-10 exerts some of its immunoregulatory functions by differential modulation of antigen presenting molecules, induced by the same combination of cytokines. 相似文献
4.
5.
6.
Henrike Rippberger Marcel M. van Gaalen Rainer K.W. Schwarting Markus W?hr 《Current Neuropharmacology》2015,13(2):220-232
Rats emit high-frequency 50-kHz ultrasonic vocalizations (USV) in appetitive situations like social interactions. Drugs of abuse are probably the most potent non-social elicitors of 50-kHz USV, possibly reflecting their euphorigenic properties. Psychostimulants induce the strongest elevation in 50-kHz USV emission, particularly amphetamine (AMPH), either when applied systemically or locally into the nucleus accumbens (Nacc). Emission of AMPH-induced 50-kHz USV depends on test context, such as the presence of conspecifics, and can be manipulated pharmacologically by targeting major neurotransmitter systems, including dopamine (DA), noradrenaline (NA), and serotonin (5-HT), but also protein kinase C (PKC) signaling. Several D1 and D2 receptor antagonists, as well as typical and atypical antipsychotics block the AMPH-induced elevation in 50-kHz USV. Inhibiting D1 and D2 receptors in the Nacc abolishes AMPH-induced 50-kHz USV, indicating a key role for this brain area. NA neurotransmission also regulates AMPH-induced 50-kHz USV emission given that α1 receptor antagonists and α2 receptor agonists exert attenuating effects. Supporting the involvement of the 5-HT system, AMPH-induced 50-kHz USV are attenuated by 5-HT2C receptor activation, whereas 5-HT2C receptor antagonism leads to the opposite effect. Finally, treatment with lithium, tamoxifen, and myricitrin was all found to result in a complete abolishment of the AMPH-induced increase in 50-kHz USV, suggesting the involvement of PKC signaling. Neurotransmitter systems involved in AMPH-induced 50-kHz USV emission only partially overlap with other AMPH-induced behaviors like hyperlocomotion. The validity of AMPH-induced 50-kHz USV as a preclinical model for neuropsychiatric disorders is discussed, particularly with relevance to altered drive and mood seen in bipolar disorder. 相似文献
7.
Nils Schweingruber Henrike J. Fischer Lisa Fischer Jens van den Brandt Anna Karabinskaya Verena Labi Andreas Villunger Benedikt Kretzschmar Peter Huppke Mikael Simons Jan P. Tuckermann Alexander Flügel Fred Lühder Holger M. Reichardt 《Acta neuropathologica》2014,127(5):713-729
Glucocorticoids (GCs) are the standard therapy for treating multiple sclerosis (MS) patients suffering from an acute relapse. One of the main mechanisms of GC action is held to be the induction of T cell apoptosis leading to reduced lymphocyte infiltration into the CNS, yet our analysis of experimental autoimmune encephalomyelitis (EAE) in three different strains of genetically manipulated mice has revealed that the induction of T cell apoptosis is not essential for the therapeutic efficacy of GCs. Instead, we identified the redirection of T cell migration in response to chemokines as a new therapeutic principle of GC action. GCs inhibited the migration of T cells towards CCL19 while they enhanced their responsiveness towards CXCL12. Importantly, blocking CXCR4 signaling in vivo by applying Plerixafor® strongly impaired the capacity of GCs to interfere with EAE, as revealed by an aggravated disease course, more pronounced CNS infiltration and a more dispersed distribution of the infiltrating T cells throughout the parenchyma. Our observation that T cells lacking the GC receptor were refractory to CXCL12 further underscores the importance of this pathway for the treatment of EAE by GCs. Importantly, methylprednisolone pulse therapy strongly increased the capacity of peripheral blood T cells from MS patients of different subtypes to migrate towards CXCL12. This indicates that modulation of T cell migration is an important mechanistic principle responsible for the efficacy of high-dose GC therapy not only of EAE but also of MS. 相似文献
8.
9.
Caroline D M Witjes Henrike E Karim-Kos Otto Visser Esther de Vries Jan N M IJzermans Robert A de Man Jan Willem W Coebergh Cornelis Verhoef 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2012,14(11):777-781
Background
To explore trends in the incidence and survival of patients with intrahepatic cholangiocarcinoma (ICC) an unselected population in Western Europe was studied.Methods
Between 1989 and 2009, all patients newly diagnosed with ICC were selected from the Netherlands Cancer Registry (n = 809). Trends in incidence, treatment and relative survival were calculated according to gender and age. Follow-up for vital status was complete until 1st January 2010.Results
The incidence rates of ICC increased significantly between 1999 and 2009, especially in the age group 45–59 years [estimated annual percentage change +3.0%, 95% confidence interval (CI) 0.2–5.8]. In the other age groups ICC incidence remained stable. Patients diagnosed with Tumour Lymph Node Metastasis (TNM) stage I mainly underwent surgery (68%), and the majority of the patients with stage II, III and IV received best supportive care (73%). One-year relative survival for patients with ICC increased significantly from 24% in 1989–1994 to 28% in 2005–2009 (P = 0.03), and corresponding 3-year relative survival improved from 4% to 8% (P = 0.02). Three-month and 1-year relative survival for patients with ICC receiving surgery was 91% and 71%, respectively.Discussion
Between 1999 and 2009, the incidence of ICC rose, especially in the age group 45–59 years, suggesting aetiological influences. Survival rates have improved during the study period. 相似文献10.