全文获取类型
收费全文 | 212篇 |
免费 | 19篇 |
国内免费 | 2篇 |
专业分类
233篇 |
出版年
2021年 | 5篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 5篇 |
2016年 | 6篇 |
2015年 | 5篇 |
2014年 | 12篇 |
2013年 | 10篇 |
2012年 | 10篇 |
2011年 | 8篇 |
2010年 | 8篇 |
2009年 | 7篇 |
2008年 | 6篇 |
2007年 | 16篇 |
2006年 | 8篇 |
2005年 | 6篇 |
2004年 | 8篇 |
2003年 | 11篇 |
2002年 | 8篇 |
2001年 | 9篇 |
2000年 | 8篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 7篇 |
1982年 | 9篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1960年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有233条查询结果,搜索用时 10 毫秒
111.
No G(i)-linked P2Y receptors have been cloned to date but the presence of such receptors is thought to be restricted to platelets and certain clonal cell lines. Using the functional approach of [(35)S]guanosine 5'-[gamma-thio]-triphosphate autoradiography, we uncovered the widespread presence of such receptors in the CNS. Under conditions in which the prominent signal due to tonic adenosine receptor activity is masked, ADP and ATP stimulated G-protein activity in multiple grey and white matter regions. Localization in the grey matter suggests inhibitory auto-/heteroreceptor function. In the white matter, activated G proteins appeared as 'hot spots' (presumed oligodendrocyte progenitors) with scattered distribution along the main fibre tracts. Responses to ATP were diminished under conditions that inhibited degradation, suggesting that prior conversion to ADP explained agonist action. Uracil nucleotides were ineffective but 2-methylthio-ADP activated G proteins approximately 500-fold more potently than ADP, although both were similarly degraded. Throughout the brain, ADP-dependent G-protein activity was reversed by 2-hexylthio-AdoOC(O)Asp(2), a non-phosphate ATP analogue, whereas selective P2Y(1) receptor antagonists proved ineffective. A similar receptor was also disclosed from the adrenal medulla. These data witness a hitherto unrecognized abundance of G(i/o)-linked ADP receptors in the nervous system. Biochemical and pharmacological behaviour suggests striking similarities to the elusive platelet P2Y(ADP) receptor. 相似文献
112.
Gas chromatographic-mass spectrometric detection of 2- and 3-hydroxy fatty acids as methyl esters from soil,sediment and biofilm 总被引:3,自引:0,他引:3
Keinänen MM Korhonen LK Martikainen PJ Vartiainen T Miettinen IT Lehtola MJ Nenonen K Pajunen H Kontro MH 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,783(2):443-451
Hydroxy fatty acids (OH-FAs) can be used in the characterization of microbial communities, especially Gram-negative bacteria. We prepared methyl esters of 2- and 3-OH-FAs from the lipid extraction residue of soil, sediment, and biofilm samples without further purification or derivatization of hydroxyl groups. OH-FA methyl esters were analyzed using a gas chromatograph equipped with a mass selective detector (GC-MS). The ions followed in MS were m/z 103 for 3-OH-FAs and m/z 90 and M-59 for 2-OH-FAs. The rapid determination of 3- and 2-OH-FAs concomitantly with phospholipid fatty acids provided more detailed information on the microbial communities present in soil, sediment, and drinking water biofilm. 相似文献
113.
Nissinen M Gylling H Vuoristo M Miettinen TA 《American journal of physiology. Gastrointestinal and liver physiology》2002,282(6):G1009-G1015
Properties of the intestinal digestion of the dietary phytosterols, cholesterol and cholestanol, and the mechanisms by which phytosterols inhibit the intestinal absorption of cholesterol in healthy human subjects are poorly known. We have studied the hydrolysis of dietary plant sterol and stanol esters and their subsequent micellar solubilization by determining their concentrations in micellar and oil phases of the jejunal contents. Two liquid formulas with low (formula 1) and high (formula 2) plant stanol concentrations were infused via a nasogastric tube to the descending duodenum of 8 healthy human subjects, and intestinal contents were sampled for gas-liquid chromatographic sterol analysis 60 cm more distally. During the duodenal transit, phytosterol esters were hydrolyzed. This was especially profound for sitostanol, as its esterified fraction per milligram of sitosterol decreased 80% (P < 0.001) in formula 1 and 61% (P < 0.001) in formula 2. Contrary to that, esterified fraction of cholesterol per milligram of sitosterol was increased fourfold (P < 0.001) in formula 1 and almost sixfold (P < 0.001) in formula 2, whereas that of cholestanol remained unchanged. Percentages of esterified sterols and stanols in total intestinal fluid samples were higher after the administration of formula 2 than of formula 1. Esterified cholesterol and stanols accumulated in the oil phase, and free stanols replaced cholesterol in the micellar phase. At high intestinal plant stanol concentrations, cholesterol looses its micellar solubility possibly by replacement of its free fraction in the micellar phase by hydrolyzed plant stanols, which leads to a decreased intestinal absorption of cholesterol. 相似文献
114.
Abstract: There are geographical regions where microbial growth in drinking waters is limited by phosphorus instead of organic carbon. In these drinking waters even a low amount of phosphorus can strongly enhance microbial growth. The formation of biofilm can be limited by low availability of phosphorus in drinking waters with low content of phosphorus. The formation of biofilms on polyvinyl chloride plates was studied in laboratory experiments with water containing 48 microg/L assimilable organic carbon and 0.19 microg/L microbially available phosphorus. We found that low additions of phosphate (1-5 microg/L PO4(3-)-P) to water increased microbial growth in the water and in the biofilm. The effect of phosphorus on microbial growth could be detected by determining either the microbial cell production or the content of ATP in biofilms. Also, in steady-state biofilms, microbial concentrations were higher with phosphorus addition as enumerated by heterotrophic plate counts on R2A-agar and acridine orange direct counting. This work confirms the earlier findings of the importance of phosphorus for microbial growth in humic-rich drinking waters. 相似文献
115.
Impaired migration and delayed differentiation of pancreatic islet cells in mice lacking EGF-receptors 总被引:11,自引:0,他引:11
Miettinen PJ Huotari M Koivisto T Ustinov J Palgi J Rasilainen S Lehtonen E Keski-Oja J Otonkoski T 《Development (Cambridge, England)》2000,127(12):2617-2627
Pancreatic acini and islets are believed to differentiate from common ductal precursors through a process requiring various growth factors. Epidermal growth factor receptor (EGF-R) is expressed throughout the developing pancreas. We have analyzed here the pancreatic phenotype of EGF-R deficient (-/-) mice, which generally die from epithelial immaturity within the first postnatal week. The pancreata appeared macroscopically normal. The most striking feature of the EGF-R (-/-) islets was that instead of forming circular clusters, the islet cells were mainly located in streak-like structures directly associated with pancreatic ducts. Based on BrdU-labelling, proliferation of the neonatal EGF-R (-/-) beta-cells was significantly reduced (2.6+/-0.4 versus 5.8+/-0.9%, P<0.01) and the difference persisted even at 7-11 days of age. Analysis of embryonic pancreata revealed impaired branching morphogenesis and delayed islet cell differentiation in the EGF-R (-/-) mice. Islet development was analyzed further in organ cultures of E12.5 pancreata. The proportion of insulin-positive cells was significantly lower in the EGF-R (-/-) explants (27+/-6 versus 48+/-8%, P<0.01), indicating delayed differentiation of the beta cells. Branching of the epithelium into ducts was also impaired. Matrix metalloproteinase (MMP-2 and MMP-9) activity was reduced 20% in EGF-R (-/-) late-gestation pancreata, as measured by gelatinase assays. Furthermore, the levels of secreted plasminogen activator inhibitor-1 (PAI-1) were markedly higher, while no apparent differences were seen in the levels of active uPA and tPa between EGF-R (-/-) and wild-type pancreata. Our findings suggest that the perturbation of EGF-R-mediated signalling can lead to a generalized proliferation defect of the pancreatic epithelia associated with a delay in beta cell development and disturbed migration of the developing islet cells as they differentiate from their precursors. Upregulated PAI-1 production and decreased gelatinolytic activity correlated to this migration defect. An intact EGF-R pathway appears to be a prerequisite for normal pancreatic development. 相似文献
116.
Myöhänen TT Venäläinen JI Tupala E Garcia-Horsman JA Miettinen R Männistö PT 《Neurochemical research》2007,32(8):1365-1374
Prolyl oligopeptidase (POP) is a serine endoprotease that hydrolyses peptides shorter than 30-mer. POP may have a role in
inositol 1,4,5-triphosphate (IP3) signaling and in the actions of antidepressants, and POP inhibitors have exhibited antiamnesic and neuroprotective properties.
However, little is known about the distribution of POP protein in the brain. We used immunohistochemistry to localize POP
enzyme in the human whole hemisphere and in the rat whole brain. In humans, the highest POP densities were observed in caudate
nucleus and putamen, hippocampus and cortex. In the rat, the highest POP densities were found in substantia nigra, hippocampus,
cerebellum and caudate putamen. In general, the distribution of POP in human and rat brains was very similar and resembled
that of IP3 receptors. Our findings are support for a role of POP in movement regulation, cognition and possibly in IP3 signaling. The expression of POP in processing nuclei further supports its function beyond neuropeptide metabolism.
Dr. Erkki Tupala M.D. sadly passed away during the research project. 相似文献
117.
对中国产丝齿菌属Hyphodontia的种类进行了研究,并记录了30个种。其中弯孢产丝齿菌Hyphodontia curvispora是中国的新记录种,热带产丝齿菌Hyphodontia tropica是首次在中国大陆的报道。根据作者的采集标本对这两个种进行了详细的描述和显微结构绘图,同时还给出了中国产丝齿菌属30个种的检索表。 相似文献
118.
Metabolic variables of cholesterol during squalene feeding in humans: comparison with cholestyramine treatment 总被引:1,自引:0,他引:1
Squalene, a key intermediate of cholesterol synthesis, is present especially in olive oil. Regulation of cholesterol metabolism by dietary squalene in man is unknown, even though olive oil users in Mediterranean areas have low serum cholesterol levels. We have investigated absorption and serum levels of squalene and cholesterol and cholesterol synthesis with the sterol balance technique and serum levels of cholesterol precursors in humans during squalene feeding (900 mg/d for 7-30 days). The results were compared with those during cholestyramine treatment. Fecal analysis suggested that about 60% of dietary squalene was absorbed. Serum squalene levels were increased 17 times, but serum triglyceride and cholesterol contents were unchanged. The squalene feeding significantly (P less than 0.05) increased serum levels of free (1.7-2.3 times) and esterified (1.9-2.4 times) methyl sterol contents, while elevations of free and esterified delta 8-cholesterol and lathosterol levels were inconsistent. Cholestyramine treatment modestly augmented free methyl sterol levels (1.3-1.7 times), less consistently than those of esterified ones, while, in contrast to the squalene feeding, serum contents of free and esterified delta 8-cholesterol and lathosterol were dramatically increased (3.3-8 times). Neither of the treatments significantly affected serum plant sterol and cholestanol levels. The squalene feeding had no consistent effect on absorption efficiency of cholesterol, but significantly increased (paired t-test, P less than 0.05) the fecal excretions of cholesterol and its nonpolar derivatives coprostanol, epicoprostanol, and coprostanone (655 +/- 83 SE to 856 +/- 146 mg/d) and bile acids (212 +/- 24 to 255 +/- 24 mg/d), indicating an increase of cholesterol synthesis by about 50%. We suggest that a substantial amount of dietary squalene is absorbed and converted to cholesterol in humans, but this squalene-induced increase in synthesis is not associated with consistent increases of serum cholesterol levels. The clearly increased serum contents of esterified methyl sterols may reflect stimulated tissue acyl CoA: cholesterol acyltransferase (ACAT, EC 2.3.1.26) activity during squalene feeding as these sterols are not esterified in serum. 相似文献
119.
Maija E. Miettinen Leena Kinnunen Jaana Leivisk? Sirkka Kein?nen-Kiukaanniemi Eeva Korpi-Hy?v?lti Leo Niskanen Heikki Oksa Timo Saaristo Jaakko Tuomilehto Mauno Vanhala Matti Uusitupa Markku Peltonen 《PloS one》2014,9(7)
Objectives
Low serum 25-hydroxyvitamin D (25OHD) level has been associated with an increased risk of several chronic diseases. Our aim was to determine lifestyle and clinical factors that are associated with 25OHD level and to investigate connection of 25OHD level with metabolic and cardiovascular disease markers.Design
In total, 2868 Finnish men and women aged 45–74 years participated in FIN-D2D population-based health survey in 2007. Participants that had a serum sample available (98.4%; n = 2822) were included in this study. 25OHD was measured with chemiluminescent microparticle immunoassay method.Results
The mean 25OHD level was 58.2 nmol/l in men (n = 1348) and 57.1 nmol/l in women (n = 1474). Mean 25OHD level was lower in the younger age groups than in the older ones (p<0.0001 both in men and women). This study confirmed that low physical activity (p<0.0001 both in men and women), smoking (p = 0.0002 in men and p = 0.03 in women) and high BMI (p<0.0001 in women) are factors that independently associate with low 25OHD level. Of the metabolic and cardiovascular disease markers high triglyceride concentration (p = 0.02 in men and p = 0.001 in women) and high apolipoprotein B/apolipoprotein A1 ratio (p = 0.04 in men and p = 0.03 in women) were independently associated with low 25OHD level.Conclusions
Higher age did not predict lower 25OHD level in this study population of aged 45–74 years which may derive from a healthy life-style of “active pensioners”. Low physical activity and smoking came up as independent lifestyle factors associated with low 25OHD level. Defining the molecular mechanisms behind the associations of 25OHD with low physical activity and smoking are important objective in future studies. The association of 25OHD with BMI, high triglyceride concentration and apolipoprotein B/apolipoprotein A1 ratio may be related to the role of vitamin D in inflammation, but more detailed studies are needed. 相似文献120.
Kristiina Rajala Bettina Lindroos Samer M. Hussein Riikka S. Lappalainen Mari Pekkanen-Mattila Jose Inzunza Bj?rn Rozell Susanna Miettinen Susanna Narkilahti Erja Kerkel? Katriina Aalto-Set?l? Timo Otonkoski Riitta Suuronen Outi Hovatta Heli Skottman 《PloS one》2010,5(4)