全文获取类型
收费全文 | 79篇 |
免费 | 6篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 1篇 |
基础医学 | 13篇 |
临床医学 | 5篇 |
内科学 | 5篇 |
神经病学 | 45篇 |
特种医学 | 2篇 |
外科学 | 3篇 |
预防医学 | 1篇 |
药学 | 6篇 |
中国医学 | 1篇 |
肿瘤学 | 1篇 |
出版年
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 3篇 |
2020年 | 1篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 2篇 |
2014年 | 5篇 |
2013年 | 4篇 |
2012年 | 8篇 |
2011年 | 6篇 |
2010年 | 1篇 |
2009年 | 3篇 |
2008年 | 4篇 |
2007年 | 2篇 |
2006年 | 3篇 |
2005年 | 4篇 |
2004年 | 2篇 |
2003年 | 2篇 |
2002年 | 1篇 |
2001年 | 2篇 |
2000年 | 7篇 |
1999年 | 4篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1985年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有85条查询结果,搜索用时 343 毫秒
11.
Appendino G Prosperini S Valdivia C Ballero M Colombano G Billington RA Genazzani AA Sterner O 《Journal of natural products》2005,68(8):1213-1217
An investigation of Thapsia garganica afforded a series of tetracyclic C-19 dilactones, whose production was dependent on the time and location of the collection. These unusual tetrahomosesquiterpenoids are presumably biosynthesized via a carbon dioxide-triggered electrophilic polyolefin cyclization. Despite the structural differences with thapsigargin, these compounds showed SERCA-inhibiting properties. 相似文献
12.
Biancolella M Valentini A Minella D Vecchione L D'Amico F Chillemi G Gravina P Bueno S Prosperini G Desideri A Federici G Bernardini S Novelli G 《Investigational new drugs》2007,25(5):491-497
Summary Androgens play an important role in controlling the growth of the normal prostate gland and in the pathogenesis of benign
prostate hyperplasia, and prostate cancer. Although testosterone is the main androgen secreted from the testes, dihydrotestosterone
(DHT), a more potent androgen converted from testosterone by 5α-reductase isozymes, type I and II, is the major androgen in
the prostate cells. The aim of this study is to investigate the cellular and molecular effects of dutasteride, a potent inhibitor
of 5α-reductase type I and type II, in androgen-responsive (LNCaP) and androgen-unresponsive (DU145) human prostate cancer(PCa)
cell lines. The expression pattern of 190 genes, selected on the basis of their proved or potential role in prostate cancerogenesis
related to androgen signalling, were analysed using a low density home-made oligoarray (AndroChip 2). Our results show that
dutasteride reduces cell viability and cell proliferation in both cell lines tested. AndroChip 2 gene signature identified
in LNCaP a total of 11 genes differentially expressed (FC ≥ ±1.5). Eight of these genes, were overexpressed and three were
underexpressed. Overexpressed genes included genes encoding for proteins involved in biosynthesis and metabolism of androgen
(HSD17B1;HSD17B3;CYP11B2), androgen receptor and androgen receptor co-regulators (AR;CCND1), and signal transduction(ERBB2; V-CAM; SOS1) whereas, underexpressed genes (KLK3; KLK2; DHCR24) were androgen-regulated genes (ARGs). No differentially expressed genes were scored in DU145. Microarray data were confirmed
by quantitative real-time PCR assay (QRT-PCR). These data offer a selective genomic signature for dutasteride treatment in
prostate epithelial cells and provide important insights in prostate cancer pathophysiology.
Supplementary Information is linked to web site 相似文献
13.
The cytotoxicity of beauvericin (BEA) on human colon adenocarcinoma (Caco-2) cells was studied as a function of time. Moreover, the oxidative damage and cell death endpoints were monitored after 24, 48 and 72 h. After BEA exposure, the IC50 values ranged from 1.9 ± 0.7 to 20.6 ± 6.9 μM. A decrease in reduced glutathione (GSH; 31%) levels, as well as an increase in oxidized glutathione (GSSG, 20%) was observed. In the presence of BEA, reactive oxygen species (ROS) level was highly increased at an early stage with the highest production of 2.0-fold higher than the control that was observed at 120 min. BEA induced cell death by mitochondria-dependent apoptotic process with loss of the mitochondrial membrane potential (ΔΨm; 9% compared to the control), increase in LPO level (from 120% to 207% compared to the control) and reduced G0/G1 phase, with an arrest in G2/M, in a dose and time-dependent manner. Cell proliferation, apoptosis and ΔΨm determined, were in a dose- time-dependent manner. Moreover, DNA damage was observed after 12.0 μM concentration. This study demonstrated that oxidative stress is one of the mechanism involved in BEA toxicity, moreover apoptosis induction and loss of ΔΨm contribute to its cytotoxicity in Caco-2 cells. 相似文献
14.
Background.— Some multiple sclerosis (MS)‐specific therapies may exacerbate a comorbid migraine. Whereas data regarding the impact of interferon beta (IFNB) on this comorbidity have been reported, studies on the role of natalizumab (NTZ) are still lacking. Purpose.— Our aim was to compare the impact of IFNB and NTZ on the frequency and disability of comorbid migraine in MS patients. Methods.— We performed a longitudinal evaluation on MS patients with comorbid migraine previously assessed at our center and retested for the present study, by comparing data from 33 patients originally treated with IFNB and thereafter switched to NTZ vs 30 patients continued currently to receive IFNB. Results.— Longitudinal analysis showed a significant reduction of migraine frequency (from a mean value of 8.4 to 5.1 days per month; P = .034) and Migraine Disability Assessment Scale (MIDAS) score (from a mean value of 14.2 to 10.5; P = .045) in the subgroup patients switched from IFNB to NTZ but not in those remaining in the IFNB recipient, irrespective of level of fatigue, trait anxiety, depression, alexithymia, or other clinical variables. Conclusions.— Our findings suggest that NTZ did not exacerbate comorbid migraine in MS patients and support the hypothesis that IFNB might represent an important trigger for migraine worsening. 相似文献
15.
16.
Grimaldi LM Prosperini L Vitello G Borriello G Fubelli F Pozzilli C 《Multiple sclerosis (Houndmills, Basingstoke, England)》2012,18(9):1337-1339
The recommended natalizumab dosage is 300 mg every 4 weeks. We evaluated radiological activity at various times from the last natalizumab infusion by examining 386 magnetic resonance imaging (MRI) scans from 166 natalizumab-treated patients with relapsing-remitting MS. Of 113 scans performed >4 weeks after last natalizumab infusion, 26 were active (i.e. had ≥1 contrast-enhancing lesions). Risk of radiological activity increased by 1.34 fold for each week of delay with respect to the recommended 4-week dosing interval, compared with schedule-adherent patients (p<0.0001). Our data suggest that an increased MRI activity ≥7 weeks from the last infusion of natalizumab should be considered in cases of therapy discontinuation. 相似文献
17.
18.
Histamine release upon adenosine 5'-monophosphate (AMP) nasal
provocation in allergic subjects 总被引:2,自引:1,他引:1 下载免费PDF全文
BACKGROUND: Nasal provocation with adenosine 5'-monophosphate (AMP) elicits nasal symptoms in subjects with rhinitis. Histamine released from mast cells may play a part in AMP induced nasal responses. METHODS: Symptoms of rhinitis were recorded and histamine release in the fluid obtained by nasal lavage after AMP, guanosine 5'-monophosphate (GMP), and placebo instillations was measured in nine subjects with allergic rhinitis and nine non-allergic controls in a double blind, randomised, placebo controlled study. RESULTS: No symptoms or significant increases in histamine were observed after GMP and placebo challenge. Significantly higher levels of histamine were seen in the nasal lavage fluids of allergic subjects following AMP challenge than in nonallergic controls, the median (range) histamine concentration increasing from the baseline value of 1.62 (0.44-6.99) ng/ml to 6.45 (0.81-16.17) ng/ml at three minutes. No increase in histamine levels was seen in the non-allergic subjects in whom the median histamine concentration was 1.13 (0.29-4.25) ng/ml at baseline and 0.97 (0.31-5.89) ng/ml three minutes after AMP challenge. CONCLUSIONS: AMP elicits an immediate rise in histamine levels in the nasal lavage fluid of allergic subjects compared with non-allergic individuals. These findings indicate that the exaggerated nasal response to adenosine may reflect mast cell priming in vivo, thus supporting its application as a potential new marker of allergic inflammation. 相似文献
19.
Lanzillo Roberta Prosperini Luca Gasperini Claudio Moccia Marcello Fantozzi Roberta Tortorella Carla Nociti Viviana Annovazzi Pietro Cavalla Paola Radaelli Marta Malucchi Simona Clerici Valentina Torri Boffa Laura Buttari Fabio Ragonese Paolo Maniscalco Giorgia Teresa Di Filippo Massimiliano Buscarinu Maria Chiara Pinardi Federica Gallo Antonio Coghe Giancarlo Pesci Ilaria Laroni Alice Gajofatto Alberto Calabrese Massimiliano Tomassini Valentina Cocco Eleonora Solaro Claudio 《Journal of neurology》2018,265(5):1174-1183
Journal of Neurology - In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying... 相似文献
20.
Pamela Latino Letizia Castelli Luca Prosperini Maria Rita Marchetti Carlo Pozzilli Morena Giovannelli 《Neurological sciences》2017,38(10):1841-1848
The purpose of the present study was to investigate the long-term persistence to treatment with botulinum toxin type A (BoNT-A) for multiple sclerosis (MS)-related spasticity and the determinants of BoNT-A discontinuation in daily clinical setting. We retrospectively collected data of patients who started BoNT-A injections and underwent regular follow-up visits. Determinants of BoNT-A discontinuation were explored in a time-to-event Cox regression analysis which included as independent variables a large set of demographic and clinical characteristics. A total of 185 patients started BoNT-A injections from 2002 to 2014 and were followed up to September 2016. Of them, data on 121 were considered in our analysis. At follow-up, 53 (44%) patients were still on treatment and 68 (56%) patients discontinued BoNT-A after a median time of 1.2 years [interval 6 months to 7.4 years]. The reasons for discontinuation were loss of efficacy (n = 45), logistic problems or barriers to reach the structure (n = 16), and adverse events (n = 7). The absence of caregiver (hazard ratio = 1.69, p = 0.03) and lack of regular rehabilitation (hazard ratio = 1.78, p = 0.02) were two independent predictors for BoNT-A discontinuation. Our study confirms the beneficial effect of combining BoNT-A injections with rehabilitation and highlights the crucial role of caregivers for achieving better long-term outcomes in people with MS suffering from spasticity. 相似文献