全文获取类型
收费全文 | 631篇 |
免费 | 31篇 |
出版年
2023年 | 5篇 |
2022年 | 18篇 |
2021年 | 24篇 |
2020年 | 15篇 |
2019年 | 15篇 |
2018年 | 24篇 |
2017年 | 24篇 |
2016年 | 32篇 |
2015年 | 39篇 |
2014年 | 48篇 |
2013年 | 53篇 |
2012年 | 73篇 |
2011年 | 67篇 |
2010年 | 27篇 |
2009年 | 28篇 |
2008年 | 33篇 |
2007年 | 26篇 |
2006年 | 35篇 |
2005年 | 16篇 |
2004年 | 18篇 |
2003年 | 17篇 |
2002年 | 12篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1978年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有662条查询结果,搜索用时 15 毫秒
51.
Reptilian transferrins: evolution of disulphide bridges and conservation of iron-binding center 总被引:1,自引:0,他引:1
Transferrins, found in invertebrates and vertebrates, form a physiologically important family of proteins playing a major role in iron acquisition and transport, defense against microbial pathogens, growth and differentiation. These proteins are bilobal in structure and each lobe is composed of two domains divided by a cleft harboring an iron atom. Vertebrate transferrins comprise of serotransferrins, lactoferrins and ovotransferrins. In mammals serotransferrins transport iron in physiological fluids and deliver it to cells, while lactoferrins scavenge iron, limiting its availability to invading microbes. In oviparous vertebrates there is only one transferrin gene, expressed either in the liver to be delivered to physiological fluids as serotransferrin, or in the oviduct with a final localization in egg white as ovotransferrin. Being products of one gene sero- and ovotransferrin are identical at the amino-acid sequence level but with different, cell specific glycosylation patterns. Our knowledge of the mechanisms of transferrin iron binding and release is based on sequence and structural data obtained for human serotransferrin and hen and duck ovotransferrins. No sequence information about other ovotransferrins was available until our recent publication of turkey, ostrich, and red-eared turtle (TtrF) ovotransferrin mRNA sequences [Ciuraszkiewicz, J., Olczak, M., Watorek, W., 2006. Isolation, cloning and sequencing of transferrins from red-eared turtle, African ostrich and turkey. Comp. Biochem. Physiol. 143 B, 301-310]. In the present paper, ten new reptilian mRNA transferrin sequences obtained from the Nile crocodile (NtrF), bearded dragon (BtrF), Cuban brown anole (AtrF), veiled and Mediterranean chameleons (VtrF and KtrF), sand lizard (StrF), leopard gecko (LtrF), Burmese python (PtrF), African house snake (HtrF), and grass snake (GtrF) are presented and analyzed. Nile crocodile and red-eared turtle transferrins have a disulphide bridge pattern identical to known bird homologues. A partially different disulphide bridge pattern was found in the Squamata (snakes and lizards). The possibility of a unique interdomain disulphide bridge was predicted for LtrF. Differences were found in iron-binding centers from those of previously known transferrins. Substitutions were found in the iron-chelating residues of StrF and TtrF and in the synergistic anion-binding residues of NtrF. In snakes, the transferrin (PtrF, HtrF and GtrF) N-lobe "dilysine trigger" occurring in all other known transferrins was not found, which indicates a different mechanism of iron release. 相似文献
52.
Grochowska Anna Dunaj Justyna Pancewicz Sławomir Czupryna Piotr Majewski Piotr Wondim Mulugeta Tryniszewska Elżbieta Moniuszko-Malinowska Anna 《Experimental & applied acarology》2022,86(4):607-607
Experimental and Applied Acarology - 相似文献
53.
54.
Dorota Pastuszak-Lewandoska Jacek Kordiak Monika Migdalska-S?k Karolina H. Czarnecka Adam Antczak Pawe? Górski Ewa Nawrot Justyna M. Kisza?kiewicz Daria Domańska Ewa Brzeziańska-Lasota 《Respiratory research》2015,16(1)
Background
Tumor suppressor gene (TSG) inactivation plays a crucial role in carcinogenesis. FUS1, NPRL2/G21 and RASSF1A are TSGs from LUCA region at 3p21.3, a critical chromosomal region in lung cancer development. The aim of the study was to analyze and compare the expression levels of these 3 TSGs in NSCLC, as well as in macroscopically unchanged lung tissue surrounding the primary lesion, and to look for the possible epigenetic mechanism of TSG inactivation via gene promoter methylation.Methods
Expression levels of 3 TSGs and 2 DNA methyltransferases, DNMT1 and DNMT3B, were assessed using real-time PCR method (qPCR) in 59 primary non-small cell lung tumors and the matched macroscopically unchanged lung tissue samples. Promoter methylation status of TSGs was analyzed using methylation-specific PCRs (MSP method) and Methylation Index (MI) value was calculated for each gene.Results
The expression of all three TSGs were significantly different between NSCLC subtypes: RASSF1A and FUS1 expression levels were significantly lower in squamous cell carcinoma (SCC), and NPRL2/G21 in adenocarcinoma (AC). RASSF1A showed significantly lower expression in tumors vs macroscopically unchanged lung tissues. Methylation frequency was 38–76 %, depending on the gene. The highest MI value was found for RASSF1A (52 %) and the lowest for NPRL2/G21 (5 %). The simultaneous decreased expression and methylation of at least one RASSF1A allele was observed in 71 % tumor samples. Inverse correlation between gene expression and promoter methylation was found for FUS1 (rs = −0.41) in SCC subtype. Expression levels of DNMTs were significantly increased in 75–92 % NSCLCs and were significantly higher in tumors than in normal lung tissue. However, no correlation between mRNA expression levels of DNMTs and DNA methylation status of the studied TSGs was found.Conclusions
The results indicate the potential role of the studied TSGs in the differentiation of NSCLC histopathological subtypes. The significant differences in RASSF1A expression levels between NSCLC and macroscopically unchanged lung tissue highlight its possible diagnostic role in lung cancer in situ recognition. High percentage of lung tumor samples with simultaneous RASSF1A decreased expression and gene promoter methylation indicates its epigenetic silencing. However, DNMT overexpression doesn’t seem to be a critical determinate of its promoter hypermethylation. 相似文献55.
56.
Lekka M Gil D Dąbroś W Jaczewska J Kulik AJ Lekki J Stachura Z Stachura J Laidler P 《Journal of molecular recognition : JMR》2011,24(5):833-842
The expression of N‐cadherin, characteristic of various cancers, very often leads to changes in the cells' adhesive properties. Thus, we sought to find out if N‐cadherin expressed in various, but cancer‐related cells, differs in its functional properties that could contribute to variations in cells' phenotypes. In our work, measurements of an unbinding force of a single N‐cadherin molecule, probed with the same antibody both on a surface of living non‐malignant (HCV29) and malignant cells (T24) of bladder cancer, were carried out with the use of an atomic force microscopy. The results show the enhanced N‐cadherin level in T24 malignant cells (8.7% vs. 3.6% obtained for non‐malignant one), confirmed by the Western blot and the immunohistochemical staining. The effect was accompanied by changes in unbinding properties of an individual N‐cadherin molecule. Lower unbinding force values (26.1 ± 7.1 pN) in non‐malignant cells reveal less stable N‐cadherin complexes, as compared to malignant cells (61.7 ± 14.6 pN). This suggests the cancer‐related changes in a structure of the binding site of the antibody, located at the extracellular domain of N‐cadherin. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
57.
Małgorzata Zalewska Justyna Lema-Rumińska Natalia Miler Magdalena Gruszka Weronika Dąbal 《In vitro cellular & developmental biology. Plant》2011,47(3):375-378
The subject of investigation was Chrysanthemum x grandiflorum (Ramat.) Kitam., ‘Satinbleu’. Leaf explants and internodes were excised from the middle part of the donor sterile plant.
Two methods of explant inoculation were applied: explants were placed polarly and horizontally. Modified MS medium (Murashige
and Skoog 1962), supplemented with 11.4 μM indoleacetic acid and 2.7 μM 6-benzylaminopurine, were prepared to induce adventitious bud formation.
Four dates of explant inoculation on the medium were tested: January 15, April 15, July 15, and October 15. Thus, regeneration
occurred in winter, spring, summer, and autumn. In the present study, a more intensive regeneration in ‘Satinbleu’ chrysanthemum
was observed in summer and autumn than in spring and winter, irrespective of the kind of explant and the inoculation method. 相似文献
58.
α,β‐Dehydroamino acid esters occur in nature. To investigate their conformational properties, a systematic theoretical analysis was performed on the model molecules Ac‐ΔXaa‐OMe [ΔXaa = ΔAla, (E)‐ΔAbu, (Z)‐ΔAbu, ΔVal] at the B3LYP/6‐311+ + G(d,p) level in the gas phase as well as in chloroform and water solutions with the self‐consistent reaction field‐polarisable continuum model method. The Fourier transform IR spectra in CCl4 and CHCl3 have been analysed as well as the analogous solid state conformations drawn from The Cambridge Structural Database. The ΔAla residue has a considerable tendency to adopt planar conformations C5 (?, ψ ≈ ? 180°, 180°) and β2 (?, ψ ≈ ? 180°, 0°), regardless of the environment. The ΔVal residue prefers the conformation β2 (?, ψ ≈ ? 120°, 0°) in a low polar environment, but the conformations α (?, ψ ≈ ? 55°, 35°) and β (?, ψ ≈ ? 55°, 145°) when the polarity increases. The ΔAbu residues reveal intermediate properties, but their conformational dispositions depend on configuration of the side chain of residue: (E)‐ΔAbu is similar to ΔAla, whereas (Z)‐ΔAbu to ΔVal. Results indicate that the low‐energy conformation β2 is the characteristic feature of dehydroamino acid esters. The studied molecules constitute conformational patterns for dehydroamino acid esters with various side chain substituents in either or both Z and E positions. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
59.
Pancer K Ciaćka A Gut W Lipka B Mierzejewska J Milewska-Bobula B Smorczewska-Kiljan A Jahnz-Rózyk K Dzierzanowska D Madaliński K Litwińska B 《Polish journal of microbiology》2011,60(3):253-258
Respiratory Syncytial Virus (RSV) is one of the most common causes of lower respiratory tract infections in young children, immunocompromised patients (children and adults), patients with chronic respiratory diseases and elderly people. Reinfections occur throughout the life, but the severity of disease decreased with subsequent infection. The aim of this study was to analyze the frequency of RSV infections in two selected subpopulations: young children (below 5 y.) and adults with chronic respiratory diseases (25-87 y.). Nasopharyngeal swabs (334) collected from October 2008 to March 2010 were examined. The presence of RSV genome was determined by RT-PCR and the presence of RSV antigen by quick immunochromatographic test. Positive results of RT-PCR were found in 45.2% of all swabs: 48.6% samples in 2008; 41.5% in 2009; 50.8% in 2010. The highest frequency of RSV-positive samples was in fall-winter months, but differences in RSV epidemic seasons were found. In the first season (2008-2009) an increased number of RSV infections was observed from November 2008, but in the second season--from January 2010. Generally, the frequency of RSV-positive RT-PCR among children was 53%, among adults 25%. The highest difference was observed in the first three-month period of 2010. RT-PCR positive samples were found in 68.5% of children and 5.9% of adults. However, the RSV antigen was found in 44.4% of samples collected from adults in this period. Our results indicate that the contribution of RSV infections during epidemic season of respiratory tract infections in Poland was really high among children and adults. 相似文献
60.
Suski M Olszanecki R Madej J Totoń-Żurańska J Niepsuj A Jawień J Bujak-Giżycka B Okoń K Korbut R 《Journal of Proteomics》2011,74(6):887-893
The involvement of both apolipoprotein E (apoE) and mitochondria in lipid metabolism is widely recognized, however there is surprisingly scarce data about the putative mitochondrial action(s) of this protein. The aim of the study was to screen the alterations in liver mitochondrial proteome caused by apoE deficiency. We applied 2DE-LC-MS/MS methodology to investigate the changes in liver mitochondrial protein expression in 6-months old apoE(-/-) mice as compared to C57BL/6J controls. ApoE(-/-), but not C57BL/6J mice developed visible atherosclerotic changes in aorta and mild, diffuse steatosis of the liver. Collectively, 18 differentially expressed proteins were identified in mitochondria, related to apoptosis, antioxidant and detoxifying mechanisms of mitochondria, as well as lipid metabolism and transport. In conclusion, differential proteomic approach revealed several lines of proteomic evidence that mitochondrial function in the liver of apoE(-/-) mice could be altered as a result of overlapping of pathological and compensatory changes in expression of proteins. 相似文献