全文获取类型
收费全文 | 338篇 |
免费 | 31篇 |
专业分类
369篇 |
出版年
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 2篇 |
2019年 | 11篇 |
2018年 | 17篇 |
2017年 | 16篇 |
2016年 | 21篇 |
2015年 | 21篇 |
2014年 | 21篇 |
2013年 | 33篇 |
2012年 | 27篇 |
2011年 | 25篇 |
2010年 | 15篇 |
2009年 | 15篇 |
2008年 | 21篇 |
2007年 | 24篇 |
2006年 | 15篇 |
2005年 | 20篇 |
2004年 | 15篇 |
2003年 | 8篇 |
2002年 | 7篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1998年 | 1篇 |
1995年 | 2篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 2篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1971年 | 1篇 |
1967年 | 1篇 |
1959年 | 1篇 |
1950年 | 2篇 |
排序方式: 共有369条查询结果,搜索用时 15 毫秒
1.
Development of physical forms of unintegrated retroviral DNA in mouse spinal cord tissue during ts1-induced spongiform encephalomyelopathy: elevated levels of a novel single-stranded form in paralyzed mice. 下载免费PDF全文
ts1 is a murine leukemia virus that causes rapidly evolving hindlimb paralysis in susceptible strains of mice. Following perinatal infection, three physical forms of unintegrated viral DNA were detected in the spinal cord by Southern blot hybridization. Linear and supercoiled closed-circle viral double-stranded DNAs were detected in both the central nervous system and non-central nervous system tissues. An elevated level of a novel minus-sense single-stranded form of viral DNA, which had a very high mobility in agarose gels, was correlated with the onset of symptoms of paralysis. As the severity of paralysis progressed, the level of this single-stranded form increased rapidly, with the highest level in the spinal cords of moribund mice. Since the virulence of a number of cytopathic retroviruses has been associated with the presence of increased amounts of unintegrated viral DNA in the tissues of the infected hosts, this novel form of highly mobile unintegrated single-stranded DNA may have a role in the neuropathogenesis of ts1. 相似文献
2.
Gendaszewska-Darmach E 《Acta biochimica Polonica》2008,55(2):227-240
Lysophospholipids have long been recognized as membrane phospholipid metabolites, but only recently lysophosphatidic acids (LPA) have been demonstrated to act on specific G protein-coupled receptors. The widespread expression of LPA receptors and coupling to several classes of G proteins allow LPA-dependent regulation of numerous processes, such as vascular development, neurogenesis, wound healing, immunity, and cancerogenesis. Lysophosphatidic acids have been found to induce many of the hallmarks of cancer including cellular processes such as proliferation, survival, migration, invasion, and neovascularization. Furthermore, autotaxin (ATX), the main enzyme converting lysophosphatidylcholine into LPA was identified as a tumor cell autocrine motility factor. On the other hand, cyclic phosphatidic acids (naturally occurring analogs of LPA generated by ATX) have anti-proliferative activity and inhibit tumor cell invasion and metastasis. Research achievements of the past decade suggest implementation of preclinical and clinical evaluation of LPA and its analogs, LPA receptors, as well as autotaxin as potential therapeutic targets. 相似文献
3.
Edyta Rytelewska Katarzyna Kisielewska Marta Kiezun Kamil Dobrzyn Marlena Gudelska Agnieszka Rak Joelle Dupont Barbara Kaminska Tadeusz Kaminski Nina Smolinska 《Molecular reproduction and development》2020,87(7):739-762
Recent studies have demonstrated that chemerin participates in the regulation of female reproductive function at the level of the ovaries. Due to the lack of data concerning the presence of the chemerin system (chemerin and its receptors: CMKLR1, GPR1, CCRL2) in the ovaries of pigs, one of the most economically important livestock species, the aim of this study was to investigate the expression and localization of chemerin and its receptors in the ovaries of prepubertal and mature gilts. We also aimed to examine the concentrations of chemerin in the follicular fluid of prepubertal and mature animals. In the present study, we have demonstrated the expression patterns of chemerin system components in the porcine follicles of different sizes of prepubertal and mature animals, as well as in corpora lutea of mature gilts during the estrous cycle and early pregnancy. The obtained results suggest that the expression of chemerin system components is influenced by the reproductive stage, cell type, and the hormonal status of gilts (the estrous cycle/pregnancy). We have also presented the localization of the chemerin system components in various ovarian structures, and also showed changes in the concentration of chemerin in the follicular fluid of pigs. The presented findings not only confirm that chemerin is produced locally in the porcine ovary but they also demonstrate that chemerin directly affects ovarian cells, as confirmed by the presence of chemerin receptors in all ovarian structures. Therefore, chemerin appears to be an important intra‐ovarian factor that could regulate ovary function in pigs. 相似文献
4.
5.
Bozena Szulc Paulina Sosicka Dorota Maszczak-Seneczko Edyta Skurska Auhen Shauchuk Teresa Olczak Hudson H. Freeze Mariusz Olczak 《The Journal of biological chemistry》2020,295(48):16445
Nucleotide sugar transporters, encoded by the SLC35 gene family, deliver nucleotide sugars throughout the cell for various glycosyltransferase-catalyzed glycosylation reactions. GlcNAc, in the form of UDP-GlcNAc, and galactose, as UDP-Gal, are delivered into the Golgi apparatus by SLC35A3 and SLC35A2 transporters, respectively. However, although the UDP-Gal transporting activity of SLC35A2 has been clearly demonstrated, UDP-GlcNAc delivery by SLC35A3 is not fully understood. Therefore, we analyzed a panel of CHO, HEK293T, and HepG2 cell lines including WT cells, SLC35A2 knockouts, SLC35A3 knockouts, and double-knockout cells. Cells lacking SLC35A2 displayed significant changes in N- and O-glycan synthesis. However, in SLC35A3-knockout CHO cells, only limited changes were observed; GlcNAc was still incorporated into N-glycans, but complex type N-glycan branching was impaired, although UDP-GlcNAc transport into Golgi vesicles was not decreased. In SLC35A3-knockout HEK293T cells, UDP-GlcNAc transport was significantly decreased but not completely abolished. However, N-glycan branching was not impaired in these cells. In CHO and HEK293T cells, the effect of SLC35A3 deficiency on N-glycan branching was potentiated in the absence of SLC35A2. Moreover, in SLC35A3-knockout HEK293T and HepG2 cells, GlcNAc was still incorporated into O-glycans. However, in the case of HepG2 cells, no qualitative changes in N-glycans between WT and SLC35A3 knockout cells nor between SLC35A2 knockout and double-knockout cells were observed. These findings suggest that SLC35A3 may not be the primary UDP-GlcNAc transporter and/or different mechanisms of UDP-GlcNAc transport into the Golgi apparatus may exist. 相似文献
6.
The chemical synthesis and cytotoxicity of new sulfur analogues of 2-methoxy-lysophosphatidylcholine
Przemysław Rytczak Anna Drzazga Edyta Gendaszewska-Darmach Andrzej Okruszek 《Bioorganic & medicinal chemistry letters》2013,23(24):6794-6798
The chemical synthesis of phosphorothioate/phosphorodithioate analogues of 2-methoxy-lysophosphatidylcholine has been described. For the preparation of new sulfur derivatives of lysophosphatidylcholine both oxathiaphospholane and dithiaphospholane approaches have been employed. Each lysophospholipid analogue was synthesized as a series of five compounds, bearing different fatty acid residues both saturated (12:0, 14:0, 16:0, 18:0) and unsaturated (18:1). The methylation of glycerol 2-hydroxyl function was applied in order to increase the stability of prepared analogues by preventing 1→2 acyl migration. The cellular toxicity of newly synthesized 2-methoxy-lysophosphatidylcholine derivatives was measured using MTT viability assay and lactate dehydrogenase release method. 相似文献
7.
Edyta Paradowska Agnieszka Jab?ońska Miros?awa Studzińska Katarzyna Skowrońska Patrycja Suski Ma?gorzata Wi?niewska-Ligier Teresa Wo?niakowska-G?sicka Dorota Nowakowska Zuzanna Gaj Jan Wilczyński Zbigniew J. Le?nikowski 《PloS one》2016,11(4)
Toll-like receptor 9 (TLR9) recognizes non-methylated viral CpG-containing DNA and serves as a pattern recognition receptor that signals the presence of human cytomegalovirus (HCMV). Here, we present the genotype distribution of single-nucleotide polymorphisms (SNPs) of the TLR9 gene in infants and the relationship between TLR9 polymorphisms and HCMV infection. Four polymorphisms (-1237T/C, rs5743836; -1486T/C, rs187084; 1174G/A, rs352139; and 2848C/T, rs352140) in the TLR9 gene were genotyped in 72 infants with symptomatic HCMV infection and 70 healthy individuals. SNP genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Digested fragments were separated and identified by capillary electrophoresis. The HCMV DNA copy number was measured by a quantitative real-time PCR assay. We found an increased frequency of heterozygous genotypes TLR9 -1486T/C and 2848C/T in infants with HCMV infection compared with uninfected cases. Heterozygous variants of these two SNPs increased the risk of HCMV disease in children (P = 0.044 and P = 0.029, respectively). In infants with a mutation present in at least one allele of -1486T/C and 2848C/T SNPs, a trend towards increased risk of cytomegaly was confirmed after Bonferroni’s correction for multiple testing (Pc = 0.063). The rs352139 GG genotype showed a significantly reduced relative risk for HCMV infection (Pc = 0.006). In contrast, the -1237T/C SNP was not related to viral infection. We found no evidence for linkage disequilibrium with the four examined TLR9 SNPs. The findings suggest that the TLR9 -1486T/C and 2848C/T polymorphisms could be a genetic risk factor for the development of HCMV disease. 相似文献
8.
Lipase‐Catalyzed Kinetic Resolution of Novel Antifungal N‐Substituted Benzimidazole Derivatives 下载免费PDF全文
Edyta Łukowska‐Chojnacka Monika Staniszewska Małgorzata Bondaryk Jan K. Maurin Maria Bretner 《Chirality》2016,28(4):347-354
A series of new N‐substituted benzimidazole derivatives was synthesized and their antifungal activity against Candida albicans was evaluated. The chemical step included synthesis of appropriate ketones containing benzimidazole ring, reduction of ketones to the racemic alcohols, and acetylation of alcohols to the esters. All benzimidazole derivatives were obtained with satisfactory yields and in relatively short times. All synthesized compounds exhibit significant antifungal activity against Candida albicans 900028 ATCC (% cell inhibition at 0.25 μg concentration > 98%). Additionally, racemic mixtures of alcohols were separated by lipase‐catalyzed kinetic resolution. In the enzymatic step a transesterification reaction was applied and the influence of a lipase type and solvent on the enantioselectivity of the reaction was studied. The most selective enzymes were Novozyme SP 435 and lipase Amano AK from Pseudomonas fluorescens (E > 100). Chirality 28:347–354, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
9.
Angelika Noga Edyta Skrzypek Marzena Warchoł Ilona Czyczyło-Mysza Kinga Dziurka Izabela Marcińska Katarzyna Juzoń Tomasz Warzecha Agnieszka Sutkowska Zygmunt Nita Krystyna Werwińska 《In vitro cellular & developmental biology. Plant》2016,52(6):590-597
Obtaining oat DH lines is only effective via wide crossing with maize. Seven hundred haploid embryos from 21 single F1 progeny obtained from wide crosses with maize were isolated, divided into four groups according to their size (<0.5 mm, 0.5–0.9 mm, 1.0–1.4 mm, and ≥1.5 mm), and transferred into 190–2 regeneration medium with different growth regulators: 0.5 mg L?1 kinetin (KIN) and 0.5 mg L?1 1-naphthaleneacetic acid (NAA); 1 mg L?1 zeatin (ZEA) and 0.5 mg L?1 NAA; or 1 mg L?1 dicamba (DIC), 1 mg L?1 picloram (PIC), and 0.5 mg L?1 kinetin (KIN). Among all isolated embryos, approximately 46.1% were between 1.0–1.4 mm, while the smallest group of embryos (7.1%) were those <0.5 mm. The ability of haploid embryos to germinate varied depending on oat genotypes and the size of embryos. Haploid embryos <0.5 mm were globular and did not germinate, whereas embryos ≥1.5 mm had clearly visible coleoptiles, radicles, and scutella, and were able to germinate. Germination of oat haploid embryos varied depending on growth regulators in the regeneration medium. Most haploid embryos germinated on medium with 0.5 mg L?1 NAA and 0.5 mg L?1 KIN, while the fewest germinated on medium with 1 mg L?1 DIC, 1 mg L?1 PIC, and 0.5 mg L?1 KIN. One hundred thirty germinated haploid embryos converted into haploid plants. Fifty oat DH lines were obtained after colchicine treatment. 相似文献
10.
Dyguda-Kazimierowicz E Sokalski WA Leszczyński J 《Journal of molecular modeling》2007,13(6-7):839-849
The subject of this study was an analysis of the role of active site residues in the phosphoryl transfer reaction catalyzed
by 4-methyl-5-β-hydroxyethylthiazole kinase (ThiK). The ThiK-catalyzed reaction is of special interest due to the lack of
a highly conserved aspartate residue serving as a catalytic base. ONIOM(B3LYP:PM3) models of stationary points along the reaction
pathway consisted of reactants, two magnesium ions and several highly conserved ThiK active site residues. The results indicate
that an SN2-like mechanism of ThiK, with γ-phosphate acting as an alcohol-activating base is reasonable. Geometries of substrates, transition
state and products were utilized in the non-empirical analysis of the physical nature of catalytic interactions taking place
in the ThiK active site. The role of particular residues was investigated in terms of their ability to preferentially stabilize
the transition state relative to substrates (differential transition state stabilization, DTSS) or products (differential
product stabilization, DPS). It seems that Mg2, Glu126 and Cys198 play a major catalytic role, whereas Mg1 and the same Cys198
are responsible for product release. It is remarkable that no dominant role of an electrostatic term in the interactions involved
in catalytic activity is observed for product release. Determination of catalytic fields expressing differential electrostatic
potential of the transition state with respect to substrates revealed the optimal electrostatic features of an ideal catalyst
for the studied reaction. The predicted catalytic environment is in agreement with experimental data showing increased catalytic
activity of ThiK upon mutation of Cys198 to aspartate.
Figure Catalytic fields for ThiK-catalyzed reaction juxtaposed with the positions of active site residues of a model system. Magnesium
ions are considered part of the transition state/reactants. The surface of constant electronic density is colored according
to differential electrostatic potential of transition state with respect to reactants. The sign of the differential potential
reflects the electrostatic properties of a complementary molecular environment. Red (green) color denotes regions where a negative (positive) charge would be optimal for catalytic activity 相似文献