全文获取类型
收费全文 | 193篇 |
免费 | 19篇 |
专业分类
212篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 4篇 |
2019年 | 1篇 |
2018年 | 8篇 |
2017年 | 4篇 |
2016年 | 2篇 |
2015年 | 9篇 |
2014年 | 6篇 |
2013年 | 9篇 |
2012年 | 12篇 |
2011年 | 11篇 |
2010年 | 12篇 |
2009年 | 10篇 |
2008年 | 6篇 |
2007年 | 9篇 |
2006年 | 11篇 |
2005年 | 11篇 |
2004年 | 2篇 |
2003年 | 10篇 |
2002年 | 10篇 |
2001年 | 10篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1993年 | 1篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1980年 | 2篇 |
1979年 | 5篇 |
1978年 | 1篇 |
1970年 | 1篇 |
1942年 | 2篇 |
排序方式: 共有212条查询结果,搜索用时 15 毫秒
51.
52.
Maarit Sillanpää Krister Melén Päivi Porkka Riku Fagerlund Kaisu Nevalainen Maija Lappalainen Ilkka Julkunen 《Virology journal》2009,6(1):1-12
Background
Light-dependent activities against enveloped viruses in St. John's Wort (Hypericum perforatum) extracts have been extensively studied. In contrast, light-independent antiviral activity from this species has not been investigated.Results
Here, we identify the light-independent inhibition of human immunodeficiency virus-1 (HIV-1) by highly purified fractions of chloroform extracts of H. perforatum. Both cytotoxicity and antiviral activity were evident in initial chloroform extracts, but bioassay-guided fractionation produced fractions that inhibited HIV-1 with little to no cytotoxicity. Separation of these two biological activities has not been reported for constituents responsible for the light-dependent antiviral activities. Antiviral activity was associated with more polar subfractions. GC/MS analysis of the two most active subfractions identified 3-hydroxy lauric acid as predominant in one fraction and 3-hydroxy myristic acid as predominant in the other. Synthetic 3-hydroxy lauric acid inhibited HIV infectivity without cytotoxicity, suggesting that this modified fatty acid is likely responsible for observed antiviral activity present in that fraction. As production of 3-hydroxy fatty acids by plants remains controversial, H. perforatum seedlings were grown sterilely and evaluated for presence of 3-hydroxy fatty acids by GC/MS. Small quantities of some 3-hydroxy fatty acids were detected in sterile plants, whereas different 3-hydroxy fatty acids were detected in our chloroform extracts or field-grown material.Conclusion
Through bioguided fractionation, we have identified that 3-hydroxy lauric acid found in field grown Hypericum perforatum has anti-HIV activity. This novel anti-HIV activity can be potentially developed into inexpensive therapies, expanding the current arsenal of anti-retroviral agents. 相似文献53.
54.
Christine A. Phillips-Krawczak Amika Singla Petro Starokadomskyy Zhihui Deng Douglas G. Osborne Haiying Li Christopher J. Dick Timothy S. Gomez Megan Koenecke Jin-San Zhang Haiming Dai Luis F. Sifuentes-Dominguez Linda N. Geng Scott H. Kaufmann Marco Y. Hein Mathew Wallis Julie McGaughran Jozef Gecz Bart van de Sluis Daniel D. Billadeau Ezra Burstein 《Molecular biology of the cell》2015,26(1):91-103
COMMD1 deficiency results in defective copper homeostasis, but the mechanism for this has remained elusive. Here we report that COMMD1 is directly linked to early endosomes through its interaction with a protein complex containing CCDC22, CCDC93, and C16orf62. This COMMD/CCDC22/CCDC93 (CCC) complex interacts with the multisubunit WASH complex, an evolutionarily conserved system, which is required for endosomal deposition of F-actin and cargo trafficking in conjunction with the retromer. Interactions between the WASH complex subunit FAM21, and the carboxyl-terminal ends of CCDC22 and CCDC93 are responsible for CCC complex recruitment to endosomes. We show that depletion of CCC complex components leads to lack of copper-dependent movement of the copper transporter ATP7A from endosomes, resulting in intracellular copper accumulation and modest alterations in copper homeostasis in humans with CCDC22 mutations. This work provides a mechanistic explanation for the role of COMMD1 in copper homeostasis and uncovers additional genes involved in the regulation of copper transporter recycling. 相似文献
55.
Yulia V. Gerasimova Petro Yakovchuk Larisa M. Dedkova Sidney M. Hecht Dmitry M. Kolpashchikov 《RNA (New York, N.Y.)》2015,21(10):1834-1843
Mutations in ribosomal RNA (rRNA) have traditionally been detected by the primer extension assay, which is a tedious and multistage procedure. Here, we describe a simple and straightforward fluorescence assay based on binary deoxyribozyme (BiDz) sensors. The assay uses two short DNA oligonucleotides that hybridize specifically to adjacent fragments of rRNA, one of which contains a mutation site. This hybridization results in the formation of a deoxyribozyme catalytic core that produces the fluorescent signal and amplifies it due to multiple rounds of catalytic action. This assay enables us to expedite semi-quantification of mutant rRNA content in cell cultures starting from whole cells, which provides information useful for optimization of culture preparation prior to ribosome isolation. The method requires less than a microliter of a standard Escherichia coli cell culture and decreases analysis time from several days (for primer extension assay) to 1.5 h with hands-on time of ∼10 min. It is sensitive to single-nucleotide mutations. The new assay simplifies the preliminary analysis of RNA samples and cells in molecular biology and cloning experiments and is promising in other applications where fast detection/quantification of specific RNA is required. 相似文献
56.
Petro Julkunen Terhi Harjula Juho Marjanen Heikki J. Helminen Jukka S. Jurvelin 《Journal of biomechanics》2009,42(5):652-656
Classically, single-phase isotropic elastic (IE) model has been used for in situ or in vivo indentation analysis of articular cartilage. The model significantly simplifies cartilage structure and properties. In this study, we apply a fibril-reinforced poroelastic (FRPE) model for indentation to extract more detailed information on cartilage properties. Specifically, we compare the information from short-term (instantaneous) and long-term (equilibrium) indentations, as described here by IE and FRPE models. Femoral and tibial cartilage from rabbit (age 0–18 months) knees (n=14) were tested using a plane-ended indenter (diameter=0.544 mm). Stepwise creep tests were conducted to equilibrium. Single-phase IE solution for indentation was used to derive instantaneous modulus and equilibrium (Young's) modulus for the samples. The classical and modified Hayes’ solutions were used to derive values for the indentation moduli. In the FRPE model, the indentation behavior was sample-specifically described with three material parameters, i.e. fibril network modulus, non-fibrillar matrix modulus and permeability. The instantaneous and fibril network modulus, and the equilibrium Young's modulus and non-fibrillar matrix modulus showed significant (p<0.01) linear correlations of R2=0.516 and 0.940, respectively (Hayes’ solution) and R2=0.531 and 0.960, respectively (the modified Hayes’ solution). No significant correlations were found between the non-fibrillar matrix modulus and instantaneous moduli or between the fibril network modulus and the equilibrium moduli. These results indicate that the instantaneous indentation modulus (IE model) provides information on tensile stiffness of collagen fibrils in cartilage while the equilibrium modulus (IE model) is a significant measure for stiffness of PG matrix. Thereby, this study highlights the feasibility of a simple indentation analysis. 相似文献
57.
58.
Hanna Isaksson Shijo Nagao Marta MaŁkiewicz Petro Julkunen Roman Nowak Jukka S. Jurvelin 《Journal of biomechanics》2010,43(12):2410-2417
Nanoindentation has recently gained attention as a characterization technique for mechanical properties of biological tissues, such as bone, on the sub-micron level. However, optimal methods to characterize viscoelastic properties of bones are yet to be established. This study aimed to compare the time-dependent viscoelastic properties of bone tissue obtained with different nanoindentation methods. Bovine cortical and trabecular bone samples (n=8) from the distal femur and proximal tibia were dehydrated, embedded and polished. The material properties determined using nanoindentation were hardness and reduced modulus, as well as time-dependent parameters based on creep, loading-rate, dissipated energy and semi-dynamic testing under load control. Each loading protocol was repeated 160 times and the reproducibility was assessed based on the coefficient of variation (CV). Additionally, three well-characterized polymers were tested and CV values were calculated for reference.The employed methods were able to characterize time-dependent viscoelastic properties of bone. However, their reproducibility varied highly (CV 9–40%). The creep constant increased with increasing dwell time. The reproducibility was best with a 30 s creep period (CV 18%). The dissipated energy was stable after three repeated load cycles, and the reproducibility improved with each cycle (CV 23%). The viscoelastic properties determined with semi-dynamic test increased with increase in frequency. These measurements were most reproducible at high frequencies (CV 9–10%). Our results indicate that several methods are feasible for the determination of viscoelastic properties of bone material. The high frequency semi-dynamic test showed the highest precision within the tested nanoindentation protocols. 相似文献
59.
Petro Julkunen Jukka S. Jurvelin Hanna Isaksson 《Biomechanics and modeling in mechanobiology》2010,9(2):237-245
Mechanical function of articular cartilage in joints between articulating bones is dependent on the composition and structure
of the tissue. The mechanical properties of articular cartilage are traditionally tested in compression using one of the three
loading geometries, i.e., confined compression, unconfined compression or indentation. The aim of this study was to utilize
a composition-based finite element model in combination with a fractional factorial design to determine the importance of
different cartilage constituents in the mechanical response of the tissue, and to compare the importance of the tissue constituents
with different loading geometries and loading rates. The evaluated parameters included water and collagen fraction as well
as fixed charge density on cartilage surface and their slope over the tissue thickness. The thicknesses of superficial and
middle zones, as based on the collagen orientation, were also included in the evaluated parameters. A three-level resolution
V fractional factorial design was used. The model results showed that inhomogeneous composition plays only a minor role in
indentation, though that role becomes more significant in confined compression and unconfined compression. In contrast, the
collagen architecture and content had a more profound role in indentation than with two other loading geometries. These differences
in the mechanical role of composition and structure between the loading geometries were emphasized at higher loading rates.
These findings highlight how the results from mechanical tests of articular cartilage under different loading conditions are
dependent upon tissue composition and structure. 相似文献
60.
Anna Hellquist Marco Zucchelli Cecilia M. Lindgren Ulpu Saarialho-Kere Tiina M. J?rvinen Sari Koskenmies Heikki Julkunen P?ivi Onkamo Tiina Skoog Jaana Panelius Anne R?is?nen-Sokolowski Taina Hasan Elisabeth Widen Iva Gunnarson Elisabet Svenungsson Leonid Padyukov Ghazaleh Assadi Linda Berglind Ville-Veikko M?kel? Katja Kivinen Andrew Wong Deborah S. Cunningham Graham Timothy J. Vyse Mauro D'Amato Juha Kere 《PloS one》2009,4(12)