全文获取类型
收费全文 | 192篇 |
免费 | 6篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2015年 | 8篇 |
2014年 | 15篇 |
2013年 | 10篇 |
2012年 | 16篇 |
2011年 | 10篇 |
2010年 | 14篇 |
2009年 | 10篇 |
2008年 | 15篇 |
2007年 | 8篇 |
2006年 | 11篇 |
2005年 | 16篇 |
2004年 | 8篇 |
2003年 | 11篇 |
2002年 | 5篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1976年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有198条查询结果,搜索用时 15 毫秒
61.
62.
Phuong Thi Mai Nguyen Megan L. Falsetta Geelsu Hwang Mireya Gonzalez-Begne Hyun Koo 《PloS one》2014,9(10)
α-Mangostin (αMG) has been reported to be an effective antimicrobial agent against planktonic cells of Streptococcus mutans, a biofilm-forming and acid-producing cariogenic organism. However, its anti-biofilm activity remains to be determined. We examined whether αMG, a xanthone purified from Garcinia mangostana L grown in Vietnam, disrupts the development, acidogenicity, and/or the mechanical stability of S. mutans biofilms. Treatment regimens simulating those experienced clinically (twice-daily, 60 s exposure each) were used to assess the bioactivity of αMG using a saliva-coated hydroxyapatite (sHA) biofilm model. Topical applications of early-formed biofilms with αMG (150 µM) effectively reduced further biomass accumulation and disrupted the 3D architecture of S. mutans biofilms. Biofilms treated with αMG had lower amounts of extracellular insoluble and intracellular iodophilic polysaccharides (30–45%) than those treated with vehicle control (P<0.05), while the number of viable bacterial counts was unaffected. Furthermore, αMG treatments significantly compromised the mechanical stability of the biofilm, facilitating its removal from the sHA surface when subjected to a constant shear stress of 0.809 N/m2 (>3-fold biofilm detachment from sHA vs. vehicle-treated biofilms; P<0.05). Moreover, acid production by S. mutans biofilms was disrupted following αMG treatments (vs. vehicle-control, P<0.05). The activity of enzymes associated with glucan synthesis, acid production, and acid tolerance (glucosyltransferases B and C, phosphotransferase-PTS system, and F1F0-ATPase) were significantly inhibited by αMG. The expression of manL, encoding a key component of the mannose PTS, and gtfB were slightly repressed by αMG treatment (P<0.05), while the expression of atpD (encoding F-ATPase) and gtfC genes was unaffected. Hence, this study reveals that brief exposures to αMG can disrupt the development and structural integrity of S. mutans biofilms, at least in part via inhibition of key enzymatic systems associated with exopolysaccharide synthesis and acidogenicity. αMG could be an effective anti-virulence additive for the control and/or removal of cariogenic biofilms. 相似文献
63.
64.
A key feature of antibodies is their ability to bind antigens with high specificity and affinity. This has led to the concept of intracellular antibodies (intrabodies), designed to mimic antibody-antigen binding, but inside cells. Antibody fragments comprising the antigen-binding variable domains are convenient formats for intrabodies, potentially allowing for intracellular functionality. Intrabodies are promising tools, capable of interfering with a wide range of molecular targets in various intracellular compartments. However, many significant challenges remain to be overcome before intrabodies can be useful therapeutic agents. Although major progress has been made in the design and selection of intrabodies, new developments and advances are needed to allow their efficient delivery and expression for treatment of human diseases. 相似文献
65.
66.
67.
UK-1 is a bis(benzoxazole) natural product displaying activity against a wide range of human cancer cell lines. A simplified analog of UK-1, 4-carbomethoxy-2-(2'-hydroxyphenyl)benzoxazole, was previously found to be almost as active as UK-1 against cancer cell lines, and similar to the natural product, formed complexes with a variety of metal ions such as Mg2+ and Zn2+. A series of 4-substituted-2-(2'-hydroxyphenyl)benzoxazole analogs of this 'minimal pharmacophore' of UK-1 were prepared. The anti-cancer activity of these analogs was examined in breast and lung cancer cell lines. Spectrophotometric titrations in methanol were carried out in order to assess the ability of UK-1 and these analogs to coordinate with Mg2+ and Cu2+ ions. Although none of the new analogs were more cytotoxic than 4-carbomethoxy-2-(2'-hydroxyphenyl)benzoxazole, some analogs were identified that display similar cytotoxicity to this simplified UK-1 analog with improved water solubility. UK-1 and all of these new analogs bind Cu2+ ions better than Mg2+ ions, and the nature of the 4-substituent is important for the Mg2+ ion binding ability of these 2-(2'-hydroxyphenyl)benzoxazoles. Previous studies of a limited number of UK-1 analogs demonstrated a correlation between Mg2+ ion binding ability and cytotoxicity; however, within this series of 4-substituted-2-(2'-hydroxyphenyl)benzoxazoles the variations in cytotoxicity do not correlate with either Mg2+ or Cu2+ ion binding ability. These results, together with recent ESI-MS studies of Cu2+-mediated DNA binding by UK-1 and analogs, indicate that UK-1 and analogs may exert their cytotoxic effects by interaction with Cu2+ or other transition metal ions, rather than Mg2+, and that metal ion-mediated DNA binding, rather than metal ion binding affinity, is important for the cytotoxic effect of these compounds. The potential role of Cu2+ ions in the cytotoxic action of UK-1 is further supported by the observation that UK-1 in the presence of Cu2+ displays enhanced cytotoxicity to MCF-7 and A549 cells when compared to UK-1 alone. 相似文献
68.
69.
Denny P Hagen FK Hardt M Liao L Yan W Arellanno M Bassilian S Bedi GS Boontheung P Cociorva D Delahunty CM Denny T Dunsmore J Faull KF Gilligan J Gonzalez-Begne M Halgand F Hall SC Han X Henson B Hewel J Hu S Jeffrey S Jiang J Loo JA Ogorzalek Loo RR Malamud D Melvin JE Miroshnychenko O Navazesh M Niles R Park SK Prakobphol A Ramachandran P Richert M Robinson S Sondej M Souda P Sullivan MA Takashima J Than S Wang J Whitelegge JP Witkowska HE Wolinsky L Xie Y Xu T Yu W Ytterberg J Wong DT 《Journal of proteome research》2008,7(5):1994-2006
Saliva is a body fluid with important functions in oral and general health. A consortium of three research groups catalogued the proteins in human saliva collected as the ductal secretions: 1166 identifications--914 in parotid and 917 in submandibular/sublingual saliva--were made. The results showed that a high proportion of proteins that are found in plasma and/or tears are also present in saliva along with unique components. The proteins identified are involved in numerous molecular processes ranging from structural functions to enzymatic/catalytic activities. As expected, the majority mapped to the extracellular and secretory compartments. An immunoblot approach was used to validate the presence in saliva of a subset of the proteins identified by mass spectrometric approaches. These experiments focused on novel constituents and proteins for which the peptide evidence was relatively weak. Ultimately, information derived from the work reported here and related published studies can be used to translate blood-based clinical laboratory tests into a format that utilizes saliva. Additionally, a catalogue of the salivary proteome of healthy individuals allows future analyses of salivary samples from individuals with oral and systemic diseases, with the goal of identifying biomarkers with diagnostic and/or prognostic value for these conditions; another possibility is the discovery of therapeutic targets. 相似文献
70.
Natividad Ramirez-Ramirez Felix Gutierrez-Corona Everardo Lopez-Romero 《Antonie van Leeuwenhoek》1993,64(1):27-33
We isolated three nikkomycin-resistant mutants of the dimorphic fungusM. rouxii which were physiologically characterized regarding their response to yeast-phase inducing conditions and their sensitivity to bacilysin. Mutant strains G21 and G23, showed a qualitatively normal, though delayed, dimorphic transition and partial cross-resistance to bacilysin. Mutant strain G27 showed an altered dimorphism, producing a high proportion (50%) of hyphal cells, and a wild-type sensitivity to bacilysin. Cell-free extracts from this mutant exhibited an activity of both basal and protease-activated chitin synthetase which was overexpressed as compared with the parental strain and mutants G21 and G23. Results are discussed in terms of the different genetic background of the mutants.Abbreviations NTG
N-methyl-N-nitro-N-nitrosoguanidine
- UDP-GlcNAc
uridine 5-diphospho-N-acetylglucosamine
- GlcNAc
N-acetylglucosamine 相似文献