全文获取类型
收费全文 | 179篇 |
免费 | 7篇 |
专业分类
186篇 |
出版年
2021年 | 2篇 |
2020年 | 2篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 1篇 |
2016年 | 5篇 |
2015年 | 6篇 |
2014年 | 14篇 |
2013年 | 14篇 |
2012年 | 11篇 |
2011年 | 11篇 |
2010年 | 11篇 |
2009年 | 8篇 |
2008年 | 9篇 |
2007年 | 11篇 |
2006年 | 10篇 |
2005年 | 3篇 |
2004年 | 9篇 |
2003年 | 8篇 |
2002年 | 17篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 1篇 |
1998年 | 5篇 |
1997年 | 5篇 |
1993年 | 2篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有186条查询结果,搜索用时 15 毫秒
81.
Bootorabi F Jänis J Hytönen VP Valjakka J Kuuslahti M Vullo D Niemelä O Supuran CT Parkkila S 《Journal of enzyme inhibition and medicinal chemistry》2011,26(6):862-870
Acetaldehyde can generate modifications in several proteins, such as carbonic anhydrase (CA) II. In this study, we extended in vitro investigations on acetaldehyde adduct formation by focusing on the other human cytosolic CA enzymes I, III, VII, and XIII. High-resolution mass spectrometric analysis indicated that acetaldehyde most efficiently formed covalent adducts with CA II and XIII. The binding of up to 19 acetaldehydes in CA II is probably attributable to the high number of lysine residues (n = 24) located mainly on the surface of the enzyme molecule. CA XIII formed more adducts (up to 25) than it contains lysine residues (n = 16) in its primary structure. Acetaldehyde treatment induced only minor changes in CA catalytic activity in most cases. The present study provides the first evidence that acetaldehyde can bind to several cytosolic CA isozymes. The functional consequences of such modifications will be further investigated in vivo by using animal models. 相似文献
82.
83.
Jarkko T. Iivarinen Rami K. Korhonen Jukka S. Jurvelin 《Computer methods in biomechanics and biomedical engineering》2016,19(10):1089-1098
Exact physiological mechanisms behind the potential positive treatment effects of pathological tissue swelling (edema), such as increased interstitial fluid flow, are poorly understood. Finite-element model was created and the model response was matched with the deformation data from the negative pressure (suction) measurements in human (N = 11) forearm. Two experimental suction protocols were simulated to evaluate their impact on interstitial fluid flow in soft tissues. Simulated continuous suction was up to 27 times more efficient in fluid transportation compared to the cyclic suction. The continuous suction that transports the interstitial fluid effectively may help to decrease soft tissue edema. 相似文献
84.
Minna M?ki Nina J?rvinen Jarkko R?bin? Christophe Roos Hannu Maaheimo Risto Renkonen 《European journal of biochemistry》2002,269(2):593-601
Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that causes severe infections in a number of hosts from plants to mammals. A-band lipopolysaccharide of P. aeruginosa contains d-rhamnosylated O-antigen. The synthesis of GDP-D-rhamnose, the d-rhamnose donor in d-rhamnosylation, starts from GDP-D-mannose. It is first converted by the GDP-mannose-4,6-dehydratase (GMD) into GDP-4-keto-6-deoxy-D-mannose, and then reduced to GDP-D-rhamnose by GDP-4-keto-6-deoxy-D-mannose reductase (RMD). Here, we describe the enzymatic characterization of P. aeruginosa RMD expressed in Saccharomyces cerevisiae. Previous success in functional expression of bacterial gmd genes in S. cerevisiae allowed us to convert GDP-D-mannose into GDP-4-keto-6-deoxy-D-mannose. Thus, coexpression of the Helicobacter pylori gmd and P. aeruginosa rmd genes resulted in conversion of the 4-keto-6-deoxy intermediate into GDP-deoxyhexose. This synthesized GDP-deoxyhexose was confirmed to be GDP-rhamnose by HPLC, matrix-assisted laser desorption/ionization time-of-flight MS, and finally NMR spectroscopy. The functional expression of P. aeruginosa RMD in S. cerevisiae will provide a tool for generating GDP-rhamnose for in vitro rhamnosylation of glycoprotein and glycopeptides. 相似文献
85.
Distribution of prolyl oligopeptidase in the mouse whole-body sections and peripheral tissues 总被引:2,自引:1,他引:1
Myöhänen TT Venäläinen JI García-Horsman JA Piltonen M Männistö PT 《Histochemistry and cell biology》2008,130(5):993-1003
Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyses proline-containing peptides shorter than 30-mer, including
many bioactive peptides. The distribution of POP in the brain has been studied but little is known about the distribution
of peripheral POP. We used immunohistochemistry to localize POP in mouse whole-body sections and at the cellular level in
peripheral tissues. Furthermore, we used a POP activity assay to reveal the associations between POP protein and its enzymatic
activity. The highest POP protein densities were found in brain, kidney, testis and thymus, but in the liver the amounts of
POP protein were small. There were remarkable differences between the distribution of POP protein and activity. The highest
POP activities were found in the liver and testis while kidney had the lowest activity. In peripheral tissues, POP was present
in various cell types both in the cytoplasm and nucleus of the cells, in contrast to the brain where no nuclear localization
was detected. These findings support the proposed role of POP in cell proliferation in peripheral tissues. The dissociation
of the distribution of POP protein and its enzymatic activity points to nonhydrolytic functions of POP and to strict endogenous
regulation of POP activity. 相似文献
86.
Jarkko I Ven?l?inen Risto O Juvonen Pekka T M?nnist? 《European journal of biochemistry》2004,271(13):2705-2715
The prolyl oligopeptidase (POP) family of serine proteases includes prolyl oligopeptidase, dipeptidyl peptidase IV, acylaminoacyl peptidase and oligopeptidase B. The enzymes of this family specifically hydrolyze oligopeptides with less than 30 amino acids. Many of the POP family enzymes have evoked pharmaceutical interest as they have roles in the regulation of peptide hormones and are involved in a variety of diseases such as dementia, trypanosomiasis and type 2 diabetes. In this study we have clarified the evolutionary relationships of these four POP family enzymes and analyzed POP sequences from different sources. The phylogenetic trees indicate that the four enzymes were present in the last common ancestor of all life forms and that the beta-propeller domain has been part of the family for billions of years. There are striking differences in the mutation rates between the enzymes and POP was found to be the most conserved enzyme of this family. However, the localization of this enzyme has changed throughout evolution, as three archaeal POPs seem to be membrane bound and one third of the bacterial as well as two eukaryotic POPs were found to be secreted out of the cell. There are also considerable distinctions between the mutation rates of the different substrate binding subsites of POP. This information may help in the development of species-specific POP inhibitors. 相似文献
87.
Alanko J Jolma P Kööbi P Riutta A Kalliovalkama J Tolvanen JP Pörsti I 《Prostaglandins, leukotrienes, and essential fatty acids》2003,69(5):345-350
The effects of chronic nitric oxide deficiency on prostacyclin and thromboxane A(2) production in vivo are unknown. Therefore, we treated rats with N(G)-nitro-L-arginine methyl ester (L-NAME), and used losartan and high calcium diet as antihypertensive treatments. Forty eight Wistar rats were divided into six groups: control; losartan (20mgkg(-1)day(-1)); high calcium diet (dietary calcium elevated from 1.1% to 3%); L-NAME (20mgkg(-1)day(-1)); losartan+L-NAME and high calcium diet+L-NAME. Prostacyclin and thromboxane A(2) production were measured after eight weeks as urinary 2,3-dinor-6-keto-PGF(1alpha) and 11-dehydro-TXB(2), respectively. Both the high calcium diet and losartan reduced blood pressure in L-NAME hypertension. Chronic nitric oxide deficiency did not modulate prostacyclin production but it nearly doubled thromboxane A(2) production in vivo. This effect was not influenced by lowering of blood pressure by blockade of angiotensin II type 1 receptors. Independent of the level of blood pressure and blockade of nitric oxide synthesis the high calcium diet decreased prostacyclin production by one third and increased thromboxane A(2) production almost two-fold in vivo. 相似文献
88.
Jolma P Kööbi P Kalliovalkama J Kähönen M Fan M Saha H Helin H Lehtimäki T Pörsti I 《American journal of physiology. Heart and circulatory physiology》2003,285(5):H1882-H1889
Chronic renal failure (CRF) is associated with abnormal lipid metabolism and high prevalence of vascular complications. Calcium salts are commonly used in CRF as phosphate binders. Increased calcium intake may also lower plasma cholesterol and beneficially influence vascular tone. Therefore, we investigated the influence of increasing dietary calcium from 0.3% to 3.0% for 8 wk after 5/6 nephrectomy (NTX) on plasma cholesterol and mesenteric resistance vessel tone in male Sprague-Dawley rats. The groups were Sham, Sham-Calcium, NTX, and NTX-Calcium (n = 10-11). Blood pressure was modestly elevated after NTX, whereas the plasma creatinine, urea nitrogen, phosphate, and parathyroid hormone levels were clearly increased. The high-calcium diet suppressed plasma phosphate and parathyroid hormone but was without effect on blood pressure. The NTX resulted in 1.6-fold elevation in plasma total cholesterol and 40% reduction in high density-to-low density lipoprotein ratio (HDL/LDL). However, the lipid profile in NTX rats on the high-calcium diet did not differ from sham-operated controls. The endothelium-mediated relaxations induced by acetylcholine were impaired in NTX rats, whereas the response was normalized by a high-calcium diet. No differences in vasorelaxations by the endothelium-independent vasodilator nitroprusside were detected. In conclusion, improved vasorelaxation after a high-calcium diet could be due to reduced plasma total cholesterol and ameliorated HDL/LDL ratio, although decreased plasma phosphate and parathyroid hormone may also play a significant role in the vascular effects of increased calcium intake. 相似文献
89.
Korhonen O Pohja S Peltonen S Suihko E Vidgren M Paronen P Ketolainen J 《AAPS PharmSciTech》2002,3(4):68-76
The aim of the study was to investigate particle and powder properties of various starch acetate powders, to study the effect
of these properties on direct compression characteristics, and to evaluate the modification opportunity of physical properties
for starch acetate powders by using various drying methods. At the end of the production phase of starch acetate, the slurry
of starch acetate was dried using various techniques. Particle, powder, and tableting properties of end products were investigated.
Particle size, circularity, surface texture, water content and specific surface area varied according to the particular drying
method of choice. However, all powders were freely flowing. Bulk and tapped densities of powders varied in the range of 0.29
to 0.44 g/cm3 and 0.39 to 0.56 g/cm3, respectively. Compaction characteristics revealed that all powders were easily deformed under compression, having yield
pressure values of less than 66 MPa according to Heckel analysis. All powders possessed a significant interparticulate bond-forming
capacity during compaction. The tensile strength values of tablets varied between 10 and 18 MPa. In conclusion, physical properties
of starch acetate could be affected by various drying techniques. A large specific surface area and water content above 4%
were favorable properties by direct compression, especially for small, irregular, and rough particles. 相似文献
90.
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