全文获取类型
收费全文 | 147篇 |
免费 | 11篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 5篇 |
2014年 | 6篇 |
2013年 | 9篇 |
2012年 | 4篇 |
2011年 | 8篇 |
2010年 | 11篇 |
2009年 | 4篇 |
2008年 | 4篇 |
2007年 | 4篇 |
2005年 | 4篇 |
2004年 | 3篇 |
2003年 | 3篇 |
2002年 | 2篇 |
2001年 | 7篇 |
2000年 | 8篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1969年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有158条查询结果,搜索用时 109 毫秒
81.
Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels 总被引:2,自引:0,他引:2
Kubben FJ Sier CF Schram MT Witte AM Veenendaal RA van Duijn W Verheijen JH Hanemaaijer R Lamers CB Verspaget HW 《Helicobacter》2007,12(5):498-504
BACKGROUND: Helicobacter pylori gastritis is recognized as an important pathogenetic factor in peptic ulcer disease and gastric carcinogenesis, and is accompanied by strongly enhanced gastric mucosal matrix metalloproteinase-9 (MMP-9) levels. AIM: This study was performed to investigate whether H. pylori-affected gastric mucosal MMP-2 and MMP-9 levels are reversible by successful treatment of the infection. PATIENTS AND METHODS: Fifty-eight patients with H. pylori-associated gastritis were treated with a combination regimen of acid inhibitory therapy and antibiotics for 14 days. The levels and isoforms of MMP-2 and MMP-9 were measured by semiquantitative gelatin-zymography, bioactivity assay and enzyme-linked immunosorbent assay in gastric mucosal biopsy homogenates. RESULTS: Latent, active, and total MMP-9 levels decreased consistently and significantly by successful H. pylori eradication, in antrum as well as corpus mucosa, compared with those prior to treatment, irrespective of the therapy regimen used. The elevated levels remained unchanged, however, when treatment failed. MMP-2 levels did not show major alterations after H. pylori therapy. CONCLUSION: Elevated MMP-9 levels in H. pylori-infected gastric mucosa are reversible by eradication of the infection. No major changes in mucosal MMP-2 levels were observed by H. pylori eradication. 相似文献
82.
Hof D Cheung K de Rooij DJ van den Hoogen FH Pruijn GJ van Venrooij WJ Raats JM 《Arthritis research & therapy》2005,7(2):R302-R309
Modifications occurring on autoantigens during cell death have been proposed to have a role in the initiation of autoimmune
diseases. Patients suffering from mixed connective tissue disease (MCTD) produce autoantibodies directed to U1 small nuclear
ribonucleoprotein (snRNP), and antibodies against a 70 kDa protein component, the U1-70K (70K) protein, are the most prominent.
During apoptosis, 70K is cleaved by caspase-3 to a 40 kDa product, which remains associated with the complex. Autoantibodies
preferentially recognizing the apoptotic form of 70K have been described previously, and an apoptosis-specific epitope on
70K has been identified. This study shows that 29 of 53 (54%) MCTD sera preferentially recognize the apoptotic form of 70K
over intact 70K. Moreover, we show that antibodies directed to an apoptosis-specific epitope on 70K are more specifically
associated with MCTD than other anti-70K antibodies, suggesting that apoptotic 70K is a better antigen for the detection of
these antibodies in MCTD patients. Longitudinal analysis of 12 MCTD patients showed in several patients that early sera are
relatively enriched with antibodies recognizing an apoptosis-specific epitope, and that the levels of these apoptosis-specific
antibodies decrease in time. These findings indicate that the early detection of apoptotic 70K is of considerable interest
for anti-U1 snRNP-positive patients. 相似文献
83.
Effects of thymoquinone on liver miRNAs and oxidative stress in Ehrlich acid mouse solid tumor model
I Meral M Pala F Akbas S Ustunova C Yildiz MH Demirel 《Biotechnic & histochemistry》2018,93(4):301-308
We investigated the effects of thymoquinone (TQ) on the expression of liver microRNAs (miRNAs), liver histopathology and oxidative stress in Ehrlich acid solid tumor model induced mice. We used 24 male BALB/c mice divided randomly into three groups. Control (C) group mice were injected intraperitoneally (i.p.) with 0.5 ml saline for four weeks. Tumor (T) group mice were injected i.p. with 0.5 ml saline for four weeks, then Ehrlich acid tumor cells were injected subcutaneously into the neck to induce solid tumor formation. TQ (T + Tq) group mice injected i.p. with 10 mg/kg TQ for four weeks, then Ehrlich acid tumor cells were injected subcutaneously into the neck of the mice in this group to induce solid tumor formation. At the end of the study, liver from all groups were removed for histopathological and miRNAs analysis, and oxidative stress measurement. We found that the expression of miR-206b-3p was up-regulated and the oxidative stress and necrosis increased in the liver tissue of mice with Ehrlich acid solid tumor. TQ application decreased the oxidative stress, prevented necrosis, increased regeneration and down-regulated the expression of miR-206b-3p in the liver tissue. 相似文献
84.
Galactosialidosis: molecular heterogeneity among distinct clinical phenotypes. 总被引:7,自引:1,他引:6 下载免费PDF全文
S Palmeri A T Hoogeveen F W Verheijen H Galjaard 《American journal of human genetics》1986,38(2):137-148
The lysosomal storage disorder galactosialidosis has been recognized as a distinct genetic and biochemical entity, associated with a combined beta-galactosidase and neuraminidase deficiency that is due to the lack of a 32-kilodalton (kDa) glycoprotein. The molecular basis of different clinical variants of galactosialidosis has been investigated. In the early-infantile form, the synthesis of the 52-kDa precursor of the 32-kDa "protective protein" is markedly reduced and the absence of the latter protein explains the severe neuraminidase deficiency. In the juvenile-adult form, there is relatively more 52-kDa precursor but no 32-kDa protein can be detected. Cells from the late-infantile form have in comparison with controls, besides a small amount of the 32-kDa glycoprotein, an accumulation of the 52-kDa precursor. Apparently, this protein is genetically altered in such a way that its further processing is impaired. Furthermore, in this mutant, the residual neuraminidase activity is stimulated four- to sixfold upon leupeptin treatment together with an increase of the 32-kDa glycoprotein. 相似文献
85.
Endotoxin induction of plasminogen activator and plasminogen activator inhibitor type 1 mRNA in rat tissues in vivo 总被引:14,自引:0,他引:14
P H Quax C M van den Hoogen J H Verheijen T Padro R Zeheb T D Gelehrter T J van Berkel J Kuiper J J Emeis 《The Journal of biological chemistry》1990,265(26):15560-15563
The tissue-specific distribution of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA) and their inhibitor type 1 (PAI-1) was analyzed at mRNA level in five major rat organ tissues. t-PA mRNA was detected in lung, kidney, heart, and liver. u-PA mRNA was detected in kidney and lung. Presence of PA mRNA correlated with the detection of PA activity in extracts of these tissues. PAI-1 mRNA was detected predominantly in heart and lung. Although PAI activity could not be measured directly in tissue extracts, the presence of PAI-1 mRNA correlated with the occurrence of PA.PAI complex in fibrin autography of tissue extracts. Endotoxin injection caused a very large increase in plasma PAI activity. This increase correlated with a marked increase in PAI-1 mRNA in nearly all tissues studied. The increase in PAI-1 mRNA is most pronounced in lung and liver. Endotoxin injection also caused an increased level of t-PA mRNA in heart and kidney, and an increased u-PA mRNA level in kidney. mRNA analysis of freshly isolated and separated subfractionated liver cells showed that the marked increase in PAI-1 mRNA in the liver after endotoxin injection may be due mainly to a strong increase of PAI-1 mRNA in the liver endothelial cells. 相似文献
86.
P H Quax E Frisdal N Pedersen S Bonavaud P Thibert I Martelly J H Verheijen F Blasi G Barlovatz-Meimon 《Developmental biology》1992,151(1):166-175
Primary cultures of human myogenic stem cells (satellite cells) mimic myogenic differentiation. During this process, the expression of the components of the plasminogen activation system underwent modulation. Activities and mRNA levels of tissue-type and urokinase-type plasminogen activator were increased in a reproducible pattern during differentiation. A modulation of the mRNA level of PAI-2 was also observed. Human satellite cells expressed a urokinase receptor and also the mRNA level of this component underwent modulation. With the exception of PAI-1 mRNA, the level of all mRNAs increased from Day 4 to Day 8, i.e., just before myoblasts fusion, and then remained high at later stages. The modulation of the plasminogen activating activity indicates that this system is directly involved in the fusion process of myogenic differentiation. 相似文献
87.
R Fingerhut G T van der Horst F W Verheijen E Conzelmann 《European journal of biochemistry》1992,208(3):623-629
Lysosomal sialidase, which was formerly believed to degrade only water-soluble substrates but not glycolipids, cleaves ganglioside substrates II3NeuNAc-LacCer, IV3NeuNAc, II3NeuNAc-GgOse4Cer, IV3 NeuNAc, II3(NeuNAc)2-GgOse4Cer when these are dispersed either with an appropriate detergent (taurodeoxycholate) or with the sulfatide activator protein, a physiologic lipid solubilizer required for the lysosomal hydrolysis of other glycolipids by water-soluble hydrolases. In the presence of the activator protein, time and protein dependence were linear within wide limits, while the detergent rapidly inactivated the enzyme. The disialo group of the b-series gangliosides was only poorly attacked by the enzyme when the lipids were dispersed with the activator protein, whereas in the presence of the detergent, they were hydrolyzed as fast as terminal sialic acid residues. With the appropriate assay method, significant ganglioside sialidase activity could be demonstrated in the secondary lysosome fraction of normal skin fibroblasts but not of sialidosis fibroblasts. Our results support the notion that there is only one lysosomal sialidase, which degrades both the water-soluble and the membrane-bound sialyl glycoconjugates. 相似文献
88.
Expression of cDNA encoding the human "protective protein" associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases 总被引:15,自引:0,他引:15
N J Galjart N Gillemans A Harris G T van der Horst F W Verheijen H Galjaard A d'Azzo 《Cell》1988,54(6):755-764
The "protective protein" is a glycoprotein that associates with lysosomal beta-galactosidase and neuraminidase and is deficient in the autosomal recessive disorder galactosialidosis. We have isolated the cDNA encoding human "protective protein". The clone recognizes a 2 kb mRNA in normal cells that is not evident in fibroblasts of an early infantile galactosialidosis patient. The cDNA directs the synthesis of a 452 amino acid precursor molecule that is processed in vivo to yield mature "protective protein," a heterodimer of 32 kd and 20 kd polypeptides held together by disulfide bridges. This mature form is also biologically functional since it restores beta-galactosidase and neuraminidase activities in galactosialidosis cells. The predicted amino acid sequence of the "protective protein" bears homology to yeast carboxypeptidase Y and the KEX1 gene product. This suggests a protease activity for the "protective protein." 相似文献
89.
M H Verheijen M Karperien U Chung M van Wijuen H Heystek J A Hendriks J M Veltmaat B Lanske E Li C W L?wik S W de Laat H M Kronenberg L H Defize 《Mechanisms of development》1999,81(1-2):151-161
A number of studies suggest a role for PTHrP and the classical PTH/PTHrP receptor (type I) in one of the first differentiation processes in mouse embryogenesis, i.e. the formation of parietal endoderm (PE). We previously reported that although in type I receptor (-/-) embryos PE formation seemed normal, the embryos were smaller from at least day 9.5 p.c. and 60% had died before day 12.5 p.c. Here we show that the observed growth defect commences even earlier, at day 8.5 p.c. Using two novel antibodies, we show that the expression of the type I receptor protein at this stage is confined to extraembryonic endoderm only. In addition, we show that large amounts of PTHrP protein are present in the adjacent trophoblast giant cells, suggesting a paracrine interaction of PTHrP and the type I PTH/PTHrP receptor in PE formation. The involvement in PE differentiation of other recently described receptors for PTHrP would explain a possible redundancy for the type I receptor in PE formation. However, deletion of the type I PTH/PTHrP receptor in ES cells by homologous recombination completely prevents PTHrP-induced PE differentiation. Based upon these observations, we propose that PTHrP and the type I PTH/PTHrP receptor, although not required for the initial formation of PE, are required for its proper differentiation and/or functioning. 相似文献
90.
Plasminogen activation by tissue activator is accelerated in the presence of fibrin(ogen) cyanogen bromide fragment FCB-2 总被引:3,自引:0,他引:3
W Nieuwenhuizen J H Verheijen A Vermond G T Chang 《Biochimica et biophysica acta》1983,755(3):531-533
Fibrin, in contrast to fibrinogen, strongly accelerates the plasminogen activation by extrinsic activator (tissue-type plasminogen activator, t-PA). However, when fibrin and fibrinogen are digested with cyanogen bromide, both digests potentiate the t-PA-mediated plasminogen activation equally well. In this report, evidence is presented that this potentiating activity resides in CNBr fragment FCB-2 (= Ho1-DSK) and that a polymeric structure such as fibrin is not a prerequisite for the potentiation. 相似文献