全文获取类型
收费全文 | 524篇 |
免费 | 37篇 |
国内免费 | 4篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 11篇 |
妇产科学 | 14篇 |
基础医学 | 77篇 |
口腔科学 | 15篇 |
临床医学 | 48篇 |
内科学 | 122篇 |
皮肤病学 | 5篇 |
神经病学 | 28篇 |
特种医学 | 32篇 |
外科学 | 53篇 |
综合类 | 6篇 |
一般理论 | 2篇 |
预防医学 | 29篇 |
眼科学 | 11篇 |
药学 | 80篇 |
中国医学 | 3篇 |
肿瘤学 | 27篇 |
出版年
2023年 | 7篇 |
2022年 | 12篇 |
2021年 | 23篇 |
2020年 | 12篇 |
2019年 | 17篇 |
2018年 | 20篇 |
2017年 | 24篇 |
2016年 | 17篇 |
2015年 | 23篇 |
2014年 | 30篇 |
2013年 | 41篇 |
2012年 | 49篇 |
2011年 | 48篇 |
2010年 | 30篇 |
2009年 | 15篇 |
2008年 | 26篇 |
2007年 | 33篇 |
2006年 | 23篇 |
2005年 | 37篇 |
2004年 | 20篇 |
2003年 | 19篇 |
2002年 | 23篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1992年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
排序方式: 共有565条查询结果,搜索用时 31 毫秒
81.
82.
Rey Romain D’Amato Thierry Boyer Laurent Brunel Lore Aouizerate Bruno Berna Fabrice Capdevielle Delphine Chereau Isabelle Chesnoy-Servanin Gabrielle Denizot Hélène Dorey Jean-Michel Dubertret Caroline Dubreucq Julien Faget Catherine Gabayet Franck Lancon Christophe Mallet Jasmina Misdrahi David Passerieux Christine Schandrin Aurélie Schürhoff Franck Urbach Mathieu Vidailhet Pierre Llorca Pierre-Michel Fond Guillaume 《European archives of psychiatry and clinical neuroscience》2017,267(6):567-577
European Archives of Psychiatry and Clinical Neuroscience - In a perspective of personalized care for smoking cessation, a better clinical characterization of smokers with schizophrenia (SZ) is... 相似文献
83.
Gojkovic-Bukarica L Savic N Peric M Markovic-Lipkovski J Cirovic S Kanjuh V Cvejic J Atanackovic M Lesic A Bumbasirevic M Heinle H 《European journal of pharmacology》2011,654(3):101-273
In order to discover an agent that can prevent spasm of the human radial artery, the aim of our study was to evaluate the effect of the K+ channel opener, pinacidil, on contractions in the radial artery. Contractions of the radial artery were evoked by exogenously applied noradrenaline or by electrical field stimulation (EFS, 20 Hz, neurogenic). Pinacidil induced concentration-dependent inhibition of both EFS- and noradrenaline-evoked contractions of the radial artery. Glibenclamide, a selective blocker of ATP-sensitive K+ channels (Kir6.x containing subunit) antagonized in the same manner the pinacidil-induced inhibition of neurogenic contractions and contractions evoked by exogenous noradrenaline. The inhibition of pinacidil relaxation by tetraethylammonium (TEA), a blocker of Ca-sensitive K+ (KCa) channels, was more pronounced in EFS-contracted preparations. A blocker of voltage-sensitive K+ (KV) channels, 4-aminopyridine (4-AP), inhibited pinacidil relaxation only in EFS-contracted preparations. In order to test the presence of different K+ channels, immunohistochemistry of K+ channels expression in the radial artery was performed. The vascular wall of the human radial artery showed variable positivity with the following applied antibodies: Kv1.2, Kv1.3, Kir6.1, and KCa1.1. The antibodies against Kv1.6, Kv2.1, and Kir6.2 channel subunits were completely negative. These results suggest that the inhibitory effect of pinacidil on contractions of the human radial artery might be postsynaptic and associated with opening of smooth muscle Kir6.1-containing KATP channels. TEA- and 4-AP-sensitive K+ channels may also contribute to pinacidil effect in the human radial artery. 相似文献
84.
Yamaleyeva LM Lindsey SH Varagic J Zhang LL Gallagher PE Chen AF Chappell MC 《Journal of cardiovascular pharmacology》2012,59(6):529-538
Salt sensitivity is a key risk factor for cardiovascular disease and renal injury. Alterations in renal nitric oxide may contribute to salt-dependent increases in blood pressure and tissue damage. Therefore, we assessed the expression of nitric oxide synthase (NOS) isoforms in the kidney and the effects of nNOS inhibition on renal injury, inflammation, and oxidative stress in the female mRen2.Lewis rat (mRen), a model of salt-sensitive hypertension. We find that a high-salt diet (4% sodium) significantly reduced endothelial NOS mRNA (2.6-fold) and protein (1.5-fold) but increased nNOS mRNA (2.4-fold) and protein (1.9-fold) in the renal cortex of these animals. Immunostaining for nNOS also seemed higher in macula densa and cortical tubules of the rats fed a high-salt diet. Circulating nitrate and nitrite levels were reduced, including the tissue levels of the NOS cofactor tetrahydrobiopterin. Cortical markers of oxidative stress (4HNE, 8-OH-deoxyguanosine) and fibrosis were increased; however, mRNA levels of the NAD(P)H oxidase components NOX4, p22phox, and p47phox were reduced. Chronic treatment with the nNOS inhibitor N-(1-Imino-3-butenyl)-L-ornithine did not influence systolic blood pressure after 4 weeks but significantly attenuated albuminuria, renal fibrosis, inflammation, and indices of oxidative stress. We conclude that an increase in nNOS expression in conjunction with reduced levels of cortical tetrahydrobiopterin may stimulate oxidative stress and renal injury in the salt-sensitive female mRen2.Lewis rat. 相似文献
85.
Tonic-Ribarska J Haxhiu A Sterjev Z Kiteva G Suturkova L Trajkovic-Jolevska S 《Acta pharmaceutica (Zagreb, Croatia)》2012,62(2):211-220
A bioanalytical HPLC method with UV detection for the determination of the antiepileptic drug valproic acid in human saliva has been developed and validated. Saliva represents an alternative matrix for therapeutic monitoring of antiepileptic drugs due to the increasing interest in free drug concentration. The proposed method involved solid-phase extraction for sample preparation and yielded very good mean recoveries of 99.4 % and 97.9 % for valproic acid and IS, respectively. The calibration function for valproic acid was linear over the concentration range of 1.0-50.0 μg mL(-1) (R(2) = 0.9989). Within-run and between-run precision and accuracy were studied at four concentrations and RSDs were less than 7.3 and 2.2 %, while accuracy values were higher than 96.8 and 97.5 %, respectively. The described method provides sensitivity, linearity, precision, accuracy and is suitable for analyses of valproic acid in saliva samples. 相似文献
86.
87.
88.
Dimitrova-Shumkovska J Veenman L Ristoski T Leschiner S Gavish M 《Toxicologic pathology》2010,38(6):957-968
7,12-Dimethylbenz[a]anthracene (DMBA) presents a pollutant implicated in various toxicological effects. The aim of this experiment was to study the effects of DMBA administration on oxidative stress, histopathological signs, and 18 kDa translocator protein (TSPO) binding characteristics in rat liver. We also studied the effects of dose stoichiometry, dose frequency, and duration of protocol of DMBA administration. In this study, rats surviving eighteen weeks after DMBA exposure showed mild to moderate histopathological changes in the liver, mainly characterized by glossy appearance of hepatocytes, heterochromatic nuclei, and glycogen overload in the midzonal region of the hepatic lobe. These changes were accompanied by significant rises in oxidant levels, along with declines in nonenzymic antioxidants, indicating that DMBA induced oxidative stress in the liver. This finding correlated well with decreases in TSPO binding capacity in the liver of the rats in our study. Other studies have shown that TSPO can be affected by oxidative stress, as well as contribute to oxidative stress at mitochondrial levels. Further studies are needed to assay whether the decreases in TSPO density in the liver are part of the damaging effects caused by DMBA or a compensatory response to the oxidative stress induced by DMBA. 相似文献
89.
Juengel E Dauselt A Makarević J Wiesner C Tsaur I Bartsch G Haferkamp A Blaheta RA 《Cancer letters》2012,324(1):83-90
Chronic mTOR inhibition may induce resistance development in renal cell carcinoma (RCC). We analyzed whether long-term exposure of RCC cells to the mTOR-inhibitor RAD001 evokes resistance and whether additional targeting histone deacetylases (HDAC) by valproic acid (VPA) overcomes RAD001 resistance. It is demonstrated that responsiveness to either drug alone is lost over time, evidenced by increased cell growth, proliferation and de-differentiation. However, drug sensitivity was conserved when RAD001 and VPA were applied in concert. Molecular analysis particularly revealed strong re-activation of Akt under chronic RAD001 or diminished histone H3 acetylation under chronic VPA single drug exposure. Combined drug application did not inactivate Akt but rather resulted in H3 acetylation remaining high while RCC cell growth was still reduced. siRNA experiments revealed that histone H3 acetylation is responsible for preserving drug sensitivity in RCCs. 相似文献
90.
Howell MD Fairchild HR Kim BE Bin L Boguniewicz M Redzic JS Hansen KC Leung DY 《The Journal of investigative dermatology》2008,128(9):2248-2258
Atopic dermatitis (AD) is an inflammatory skin disease associated with frequent skin infection and impaired skin barrier function. Recent studies indicate that increased Th2 cytokine expression contributes to reduction in antimicrobial peptides and reduced filaggrin (FLG) expression, however, the mechanisms leading to this effect is unknown. Using proteomics, we found the S100 calcium-binding protein A11 (S100/A11) to be significantly downregulated in the presence of IL-4 and IL-13. Culturing keratinocytes with increased calcium concentrations significantly induced S100/A11 expression. This corresponded with an increase in human beta-defensin (HBD)-3 and FLG expression. Interference of S100/A11 expression, by siRNA, inhibited induction of HBD-3 and FLG. Furthermore p21, a cyclin-dependent kinase inhibitor downstream of S100/A11, was required for calcium-mediated induction of HBD-3 and FLG. Importantly, transduction of p21-recombinant protein into keratinocytes prevented IL-4/IL-13-mediated inhibition of FLG and HBD-3 expression. S100/A11 and p21 gene expression was also found to be significantly lower in acute and chronic AD skin. This study demonstrates an important role for S100/A11 and p21 in regulating skin barrier integrity and the innate immune response. 相似文献