全文获取类型
收费全文 | 1034篇 |
免费 | 85篇 |
专业分类
1119篇 |
出版年
2023年 | 2篇 |
2022年 | 7篇 |
2021年 | 22篇 |
2020年 | 6篇 |
2019年 | 15篇 |
2018年 | 29篇 |
2017年 | 18篇 |
2016年 | 35篇 |
2015年 | 53篇 |
2014年 | 58篇 |
2013年 | 99篇 |
2012年 | 80篇 |
2011年 | 87篇 |
2010年 | 67篇 |
2009年 | 53篇 |
2008年 | 57篇 |
2007年 | 66篇 |
2006年 | 62篇 |
2005年 | 55篇 |
2004年 | 38篇 |
2003年 | 49篇 |
2002年 | 50篇 |
2001年 | 13篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 7篇 |
1996年 | 2篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 6篇 |
1992年 | 13篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 6篇 |
1987年 | 1篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
排序方式: 共有1119条查询结果,搜索用时 15 毫秒
81.
Romani R Antognelli C Baldracchini F De Santis A Isani G Giovannini E Rosi G 《Chemico-biological interactions》2003,145(3):321-329
The present study looks at possible changes in the activity of acetylcholinesterase (AChE) in tissues (brain and white muscle) of the Mediterranean bony fish Sparus auratus after a 20 days exposure to sublethal concentrations (0.1 or 0.5 ppm) of copper in the marine water and on control untreated animals. The trials also included measurements of Cu concentration in the tissues to evaluate possible metal accumulation. Moreover, sedimentation analysis as well as V(max) and K(m) determination were carried out in tissue extracts of Cu-exposed or control animals. V(max) and K(m) were also determined with or without addition of Cu(2+) in the assay. No Cu accumulation occurred in brain and muscle after Cu exposure. AChE showed in both tissues a molecular polymorphism with putative globular (G) and asymmetric (A) forms. Cu exposition led to an increased specific activity and improved catalytic efficiency of AChE in brain and muscle, seemingly regarding G forms. The increase in catalytic efficiency also resulted from the in vitro assay with tissue extracts and Cu(2+) addition. The higher AChE activity and catalytic efficiency in both tissues after Cu exposition and without metal accumulation, suggests an increase of free Cu aliquot into the cells, likely due to mechanisms of metal homeostasis. 相似文献
82.
Lutgarde Thijs Jan A Staessen Sonia Beleva Willem H Birkenhäger Christopher J Bulpitt Hilde Celis Astrid E Fletcher Rumjana Kermova Gastone Leonetti Tovio Laks Stefan Mantov Choudomir Nachev Cinzia Sarti Jaakko Tuomilehto Robert H Fagard 《Trials》2001,2(6):1-9
Background
The randomised, double-blind, placebo-controlled Systolic Hypertension in Europe trial (Syst-Eur 1) proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. In an attempt to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine, the Syst-Eur patients remained in open follow-up after the end of Syst-Eur 1. This paper presents the second progress report of this follow-up study (Syst-Eur 2). It describes BP control and adherence to study medications.Methods
After the end of Syst-Eur 1 all patients, treated either actively or with placebo, were invited either to continue or to start antihypertensive treatment with the same drugs as previously used in the active treatment arm. In order to reach the target BP (sitting SBP <150 mmHg), the first line agent, nitrendipine, could be associated with enalapril and/or hydrochlorothiazide.Results
Of the 3787 eligible patients, 3516 (93%) entered Syst-Eur 2. At the last available visit, 72% of the patients were taking nitrendipine. SBP/DBP at entry in Syst-Eur 2 averaged 160/83 mmHg in the former placebo group and 151/80 mmHg in the former active-treatment group. At the last follow-up visit SBP/DBP in the patients previously randomised to placebo or active treatment had decreased by 16/5 mmHg and 7/5 mmHg, respectively. The target BP was reached by 74% of the patients.Conclusion
Substantial reductions in systolic BP may be achieved in older patients with isolated systolic hypertension with a treatment strategy starting with the dihydropyridine calcium-channel blocker, nitrendipine, with the possible addition of enalapril and/or hydrochlorothiazide. 相似文献83.
Manfredini R Gallerani M Boari B Maraldi C la Cecilia O Rafael Ferreira AB Smolensky MH Portaluppi F 《Chronobiology international》2002,19(4):785-791
The aim of this study was to examine 24h patterning in the symptoms indicative of third-degree atrio-ventricular (AV) heart block. We found a total of 227 cases (126 men and 101 women) of third-degree AV block that had been diagnosed by the Emergency Medical Department of the St. Anna Hospital in Ferrara, Italy between 1990 and 2001. Determination of the hour of onset of symptomatic third-degree AV block, however, was possible and listed in the records of only 161 or 70.9% of the cases (92 men and 69 women). The onset time of every event was categorized into one of four 6h spans of the 24h: night (00:00-05:59h), morning (06:00-11:59h), afternoon (12:00-17:59h), and evening (18:00-23:59h). The onset of the symptoms of third-degree AV block in the sample of 161 cases was significantly greater in the morning between 06:00 and 11:59h than any other 6h span of the day and night (chi2-test; p < 0.001). The same phenomenon was substantiated in the subgroup of the 92 males (chi2; p < 0.0001), although it could not be detected for the smaller subgroup of 69 women. The 24h pattern, with morning preference, in the onset of symptomatic third-degree AV block is similar to the one in sudden cardiac death and cardiogenic cardiac arrest. The etiology of the 24h pattern in symptomatic AV block is unknown; it may be an expression of intrinsic biological rhythmicity within the heart tissue or its control system, and/or the timing of environmental triggers resulting in coronary ischemia. 相似文献
84.
85.
Brambilla G Civitareale C Ballerini A Fiori M Amadori M Archetti LI Regini M Betti M 《Redox report : communications in free radical research》2002,7(3):159-163
In pigs, the genetic selection for lean, large muscle blocks and fast growth has been linked to an increased prevalence of metabolic diseases such as porcine stress syndrome and mulberry heart disease. These diseases are associated with cardiovascular inadequacy, which may lead to oxidative stress. In the present study, reactive oxygen metabolites (ROMs) and the anti-oxidant power (OXY) in sera of different swine groups were investigated. The following groups were selected (each around 80 kg body weight): wild boars (WB), Cinta Senese (CS), and Landrace x Large White (LxLW), the latter as both specific pathogen-free (SPF) and intensively farmed animals. In addition, a group of LxLW agonic sows (AS) was also investigated; this group is known to be under oxidative stress. Two colorimetric micro-methods were used to measure ROMs and OXY; ROMs were expressed as mM H(2)O(2) and OXY as microM HOCl neutralised. Between groups, average ROM and OXY values were found to be significantly different by one-way ANOVA (P < 0.001). ROM levels were lower in WB (13.41 +/- 1.85) and CS (19.27 +/- 1.68), and highest in LxLW (42.00 +/- 1.36). OXY values ranged from 260.10 +/- 22.13 (WB) to 396.90 +/- 9.83 (LxLW). Only one swine group (the CS group) showed a significant, positive correlation between ROM and OXY values. The AS group even showed a negative correlation between ROM and OXY values. These results imply satisfactory environmental coping occurred only within the CS group. Results are discussed in the light of animal welfare legislation, food safety and consumers' protection. 相似文献
86.
Mechanisms transducing the aldosterone secretagogue signal of endothelins in the human adrenal cortex 总被引:1,自引:0,他引:1
Evidence has been provided that the 21-amino acid hypertensive peptide endothelin (ET)-1 exerts a potent secretagogue effect on human adrenocortical zona glomerulosa (ZG), acting through two receptor subtypes, called ET(A) and ET(B), the signaling mechanism(s) of which has (have) not yet been investigated. Collagenase dispersed human ZG cells were obtained from normal adrenals of patients undergoing nephrectomy/adrenalectomy for renal cancer. The selective ET(A)- and ET(B)-receptor activation was obtained by exposing dispersed cells to ET-1 plus the ET(B)-receptor antagonist BQ-788 and to the ET(B)-receptor agonist BQ-3020, respectively. The phospholipase (PL) C inhibitor U-73122 abolished ET(A) receptor-mediated secretory response, but only partially prevented the ET(B) receptor-mediated one. The phosphatidylinositol 3-kinase inhibitor wortmannin, the calmodulin inhibitor W-7 and the protein kinase (PK) C inhibitor calphostin-C significantly blunted the secretory responses ensuing from the activation of both receptor subtypes. When added together, calphostin-C and wortmannin or W-7 abolished ET(A)-mediated secretory response, but only decreased ET(B)-mediated one. The ET(B) receptor-, but not the ET(A) receptor-mediated aldosterone response was partially reversed by the cyclooxygenase (COX) inhibitor indomethacin, which when added together with U-73122 abolished it. ET(A)-receptor activation raised inositol triphosphate (IP(3)) production from dispersed ZG cells, while ET(B)-receptor stimulation enhanced both IP(3) and prostaglandin-E(2) production. Collectively, our findings indicate that ETs stimulate aldosterone secretion from human ZG cells, acting through ET(A) receptors exclusively coupled to PLC/PKC-dependent pathway and ET(B) receptors coupled to both PLC/PKC- and COX-dependent cascades. 相似文献
87.
Feinstein DL Heneka MT Gavrilyuk V Dello Russo C Weinberg G Galea E 《Neurochemistry international》2002,41(5):357-365
It is now well accepted that inflammatory events contribute to the pathogenesis of numerous neurological disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease, and AID's dementia. Whereas inflammation in the periphery is subject to rapid down regulation by increases in anti-inflammatory molecules and the presence of scavenging soluble cytokine receptors, the presence of an intact blood-brain barrier may limit a similar autoregulation from occurring in brain. Mechanisms intrinsic to the brain may provide additional immunomodulatory functions, and whose dysregulation could contribute to increased inflammation in disease. The findings that noradrenaline (NA) reduces cytokine expression in microglial, astroglial, and brain endothelial cells in vitro, and that modification of the noradrenergic signaling system occurs in some brain diseases having an inflammatory component, suggests that NA could act as an endogenous immunomodulator in brain. Furthermore, accumulating studies indicate that modification of the noradrenergic signaling system occurs in some neurodiseases. In this article, we will briefly review the evidence that NA can modulate inflammatory gene expression in vitro, summarize data supporting a similar immunomodulatory role in brain, and present recent data implicating a role for NA in attenuating the cortical inflammatory response to beta amyloid protein. 相似文献
88.
89.
Galea E Heneka MT Dello Russo C Feinstein DL 《Cellular and molecular neurobiology》2003,23(4-5):625-635
It is now well accepted that inflammatory responses in brain contribute to the genesis and evolution of damage in neurological diseases, trauma, and infection. Inflammatory mediators including cytokines, cell adhesion molecules, and reactive oxygen species including NO are detected in human brain and its animal models, and interventions that reduce levels or expression of these agents provide therapeutic benefit in many cases. Although in some cases, the causes of central inflammatory responses are clear—for example those due to viral infection in AIDS dementia, or those due to the secretion of proinflammatory substances by activated lymphocytes in multiple sclerosis—in other conditions the factors that allow the initiation of brain inflammation are not well understood; nor is it well known why brain inflammatory activation is not as well restricted as it is in the periphery. The concept is emerging that perturbation of endogenous regulatory mechanisms could be an important factor for initiation, maintenance, and lack of resolution of brain inflammation. Conversely, activation of intrinsic regulatory neuronal pathways could provide protection in neuroinflammatory conditions. This concept is the extension of the principle of central neurogenic neuroprotection formulated by Donald Reis and colleagues, which contends the existence of neuronal circuits that protect the brain against the damage initiated by excitotoxic injury. In this paper we will review work initiated in the Reis laboratory establishing that activation of endogenous neural circuits can exert anti-inflammatory actions in brain, present data suggesting that these effects could be mediated by noradrenaline, and summarize recent studies suggesting that loss of noradrenergic locus ceruleus neurons contributes to inflammatory activation in Alzheimer's disease. 相似文献
90.
Double muscling in Marchigiana beef breed is caused by a stop codon in the third exon of myostatin gene 总被引:10,自引:0,他引:10
Cinzia?MarchitelliEmail author Maria?Carmela?Savarese Alessandra?Crisà Alessandro?Nardone Paolo?Ajmone?Marsan Alessio?Valentini 《Mammalian genome》2003,14(6):392-395
Double muscling is a partially recessive trait present in some beef breeds. It shows a high frequency in some breeds, while in others the frequency is low, and double-muscled individuals are rare. The double muscling is caused by an allelic series of mutations that cause a loss of function of the myostatin gene ( GDF8). We describe here a new mutation in the myostatin gene in Marchigiana breed, a typical beef breed of Central Italy, in which rare double-muscling individuals have been described. A PCR product of the third exon was sequenced in subjects phenotypically showing double muscling, and a G > T transversion was discovered that introduces a premature stop codon. The variant found adds to the large series of mutations present in cattle, and particularly to the only two causative of double muscling in the third exon. A PCR-RFLP test is described for the rapid and effective identification of both heterozygous and homozygous subjects. It was applied to a larger survey carried on the same and also in two other beef breeds, Chianina and Romagnola. Further individuals carrying the new variant were found in Marchigiana, but none in the other breeds. The results may be important for a better comprehension of the role of myostatin in muscular development, for commercial use and for the inference of phylogeny of this gene. 相似文献