全文获取类型
收费全文 | 202篇 |
免费 | 19篇 |
出版年
2022年 | 1篇 |
2021年 | 6篇 |
2020年 | 6篇 |
2019年 | 10篇 |
2018年 | 7篇 |
2017年 | 5篇 |
2016年 | 9篇 |
2015年 | 10篇 |
2014年 | 5篇 |
2013年 | 3篇 |
2012年 | 9篇 |
2011年 | 9篇 |
2010年 | 10篇 |
2009年 | 7篇 |
2008年 | 5篇 |
2007年 | 3篇 |
2006年 | 8篇 |
2005年 | 11篇 |
2004年 | 4篇 |
2003年 | 15篇 |
2002年 | 8篇 |
2001年 | 7篇 |
2000年 | 13篇 |
1999年 | 8篇 |
1998年 | 8篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 6篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有221条查询结果,搜索用时 843 毫秒
91.
Evolutionary lineages of several limnic gastropod genera (Viviparus, Melanopsis, Theodoxus) from the Neogene of Kos island (Dodecanese, Greece) are described and interpreted. The attempt is made to analyse the paleoecological development of a limnic sedimentary basin in the eastern portion of Kos by means of Diatoms. Obviously, there is no relation between the chemical parameters of the water of the former lake and the morphological development of the gastropods. The lineages of Viviparus brevis, Theodoxus doricus and Melanopsis gorceixi are suggested to be caused by phyletic transformations and not by changing environmental conditions. It is, thus, possible to establish a local biostratigraphy based on subspecies, and moreover, a more regional one based on longer ranging species. 相似文献
92.
Metabolism of cationized lipoproteins by human fibroblasts: biochemical and morphologic correlations
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Human plasma low density lipoprotein (LDL) that had been rendered polycationic by coupling with N, N-dimethyl-1, 3-propanediamine (DMPA) was shown by electron microscopy to bind in clusters to the surface of human fibroblasts. The clusters resembled those formed by polycationic ferritin (DMPA-feritin), a visual probe that binds to anionic site on the plasma membrane. Biochemical studies with (125)I-labeled DMPA-LDL showed that the membrane-bound lipoprotein was internalized and hydrolyzed in lysosomes. The turnover time for cell bound (125)I-DMPA-LDL, i.e., the time in which the amount of (125)I-DMPA-LDL degraded was equal to the steady-state cellular content of the lipoprotein, was about 50 h. Because the DMPA-LDL gained access to fibroblasts by binding nonspecifically to anionic sites on the cell surface rather than by binding to the physiologic LDL receptor, its uptake failed to be regulated under conditions in which the uptake of native LDL was reduced by feedback suppression of the LDL receptor. As a result, unlike the case with native LDL, the DMPA-LDL accumulated progressively within the cell, and this led to a massive increase in the cellular content of both free and esterified cholesterol. Studies with (14)C-oleate showed that at least 20 percent of the accumulated cholesteryl esters represented cholesterol that had been esterified within the cell. After 4 days of incubation with 10 μg/ml of DMPA-LDL, fibroblasts had accumulated so much cholesteryl ester that neutral lipid droplets were visible at the light microscope level with Oil Red O staining. By electron microscopy, these intracellular lipid droplets were observed to lack a tripartite limiting membrane. The ability to cause the overaccumulation of cholesteryl esters within cells by using DMPA-LDL provides a model system for study of the pathologic consequences at the cellular level of massive deposition of cholesteryl ester. 相似文献
93.
The Sleep-inducing Lipid Oleamide Deconvolutes Gap Junction Communication and Calcium Wave Transmission in Glial Cells 总被引:6,自引:1,他引:5
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Xiaojun Guan Benjamin F. Cravatt George R. Ehring James E. Hall Dale L. Boger Richard A. Lerner Norton B. Gilula 《The Journal of cell biology》1997,139(7):1785-1792
Oleamide is a sleep-inducing lipid originally isolated from the cerebrospinal fluid of sleep-deprived cats. Oleamide was found to potently and selectively inactivate gap junction–mediated communication between rat glial cells. In contrast, oleamide had no effect on mechanically stimulated calcium wave transmission in this same cell type. Other chemical compounds traditionally used as inhibitors of gap junctional communication, like heptanol and 18β-glycyrrhetinic acid, blocked not only gap junctional communication but also intercellular calcium signaling. Given the central role for intercellular small molecule and electrical signaling in central nervous system function, oleamide- induced inactivation of glial cell gap junction channels may serve to regulate communication between brain cells, and in doing so, may influence higher order neuronal events like sleep induction. 相似文献
94.
Patterns of differentiation and hybridization in North American wolflike canids, revealed by analysis of microsatellite loci 总被引:8,自引:0,他引:8
Roy MS; Geffen E; Smith D; Ostrander EA; Wayne RK 《Molecular biology and evolution》1994,11(4):553-570
Genetic divergence and gene flow among closely related populations are
difficult to measure because mutation rates of most nuclear loci are so low
that new mutations have not had sufficient time to appear and become fixed.
Microsatellite loci are repeat arrays of simple sequences that have high
mutation rates and are abundant in the eukaryotic genome. Large population
samples can be screened for variation by using the polymerase chain
reaction and polyacrylamide gel electrophoresis to separate alleles. We
analyzed 10 microsatellite loci to quantify genetic differentiation and
hybridization in three species of North American wolflike canids. We
expected to find a pattern of genetic differentiation by distance to exist
among wolflike canid populations, because of the finite dispersal distances
of individuals. Moreover, we predicted that, because wolflike canids are
highly mobile, hybrid zones may be more extensive and show substantial
changes in allele frequency, relative to nonhybridizing populations. We
demonstrate that wolves and coyotes do not show a pattern of genetic
differentiation by distance. Genetic subdivision in coyotes, as measured by
theta and Gst, is not significantly different from zero, reflecting
persistent gene flow among newly established populations. However, gray
wolves show significant subdivision that may be either due to drift in past
Ice Age refugia populations or a result of other causes. Finally, in areas
where gray wolves and coyotes hybridize, allele frequencies of gray wolves
are affected, but those of coyotes are not. Past hybridization between the
two species in the south-central United States may account for the origin
of the red wolf.
相似文献
95.
Changgui Shi MD Vaskar Das PhD Xin Li MD PhD Ranjan Kc PhD Sujun Qiu MD InSug O‐Sullivan PhD Richard L. Ripper CVT Jeffrey S. Kroin PhD Fackson Mwale PhD Atiyayein A. Wallace MS Bingqian Zhu MSN Lan Zhao PhD Andre J. van Wijnen PhD Mingliang Ji MD PhD Jun Lu MD PhD Gina Votta‐Velis MD PhD Wen Yuan MD Hee‐Jeong Im PhD 《Journal of cellular physiology》2018,233(10):6589-6602
96.
The three-dimensional structures of the complexes of the aspartic proteinase from Rhizopus chinensis (Rhizopuspepsin, EC 3.4.23.6) with pepstatin and two pepstatin-like peptide inhibitors of renin have been determined by X-ray diffraction methods and refined by restrained least-squares procedures. The inhibitors adopt an extended conformation and lie in the deep groove located between the two domains of the enzyme. Inhibitor binding is accompanied by a conformational change at the "flap," a beta-hairpin loop region, that projects over the binding cleft and closes down over the inhibitor, excluding water molecules from the vicinity of the scissile bond. The hydroxyl group of the central statyl residue of the inhibitors replaces the water molecule found between the two active aspartates, Asp-35 and Asp-218, in the native structure. The refined structures provide additional data to define the specific subsites of the enzyme and also show a system of hydrogen bonding to the inhibitor backbone similar to that observed for a reduced inhibitor. 相似文献
97.
Dale L. Boger Robert M. Borzilleri Seiji Nukui 《Bioorganic & medicinal chemistry letters》1995,5(24):3091-3096
Synthesis of appropriately and fully functionalized 16-membered CD and DE ring systems of vancomycin is detailed. 相似文献
98.
Raffael AC Oliveira Ricardo VM Almeida Márcia DA Dantas Felipe N Castro Jo?o Paulo MS Lima Daniel CF Lanza 《BMC bioinformatics》2014,15(1)
Background
The PCR technique and its variations have been increasingly used in the clinical laboratory and recent advances in this field generated new higher resolution techniques based on nucleic acid denaturation dynamics. The principle of these new molecular tools is based on the comparison of melting profiles, after denaturation of a DNA double strand. Until now, the secondary structure of single-stranded nucleic acids has not been exploited to develop identification systems based on PCR. To test the potential of single-strand RNA denaturation as a new alternative to detect specific nucleic acid variations, sequences from viruses of the Totiviridae family were compared using a new in silico melting curve approach. This family comprises double-stranded RNA virus, with a genome constituted by two ORFs, ORF1 and ORF2, which encodes the capsid/RNA binding proteins and an RNA-dependent RNA polymerase (RdRp), respectively.Results
A phylogenetic tree based on RdRp amino acid sequences was constructed, and eight monophyletic groups were defined. Alignments of RdRp RNA sequences from each group were screened to identify RNA regions with conserved secondary structure. One region in the second half of ORF2 was identified and individually modeled using the RNAfold tool. Afterwards, each DNA or RNA sequence was denatured in silico using the softwares MELTSIM and RNAheat that generate melting curves considering the denaturation of a double stranded DNA and single stranded RNA, respectively. The same groups identified in the RdRp phylogenetic tree were retrieved by a clustering analysis of the melting curves data obtained from RNAheat. Moreover, the same approach was used to successfully discriminate different variants of Trichomonas vaginalis virus, which was not possible by the visual comparison of the double stranded melting curves generated by MELTSIM.Conclusion
In silico analysis indicate that ssRNA melting curves are more informative than dsDNA melting curves. Furthermore, conserved RNA structures may be determined from analysis of individuals that are phylogenetically related, and these regions may be used to support the reconstitution of their phylogenetic groups. These findings are a robust basis for the development of in vitro systems to ssRNA melting curves detection.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-243) contains supplementary material, which is available to authorized users. 相似文献99.
Cheng H Chong Y Hwang I Tavassoli A Zhang Y Wilson IA Benkovic SJ Boger DL 《Bioorganic & medicinal chemistry》2005,13(10):3577-3585
The synthesis and evaluation of 10-methanesulfonyl-DDACTHF (1), 10-methanesulfonyl-5-DACTHF (2), and 10-methylthio-DDACTHF (3) as potential inhibitors of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase) are reported. The compounds 10-methanesulfonyl-DDACTHF (1, K(i) = 0.23 microM), 10-methanesulfonyl-5-DACTHF (2, K(i) = 0.58 microM), and 10-methylthio-DDACTHF (3, K(i) = 0.25 microM) were found to be selective and potent inhibitors of recombinant human GAR Tfase. Of these, 3 exhibited exceptionally potent, purine sensitive growth inhibition activity (3, IC50 = 100 nM) against the CCRF-CEM cell line being 3-fold more potent than Lometrexol and 30-fold more potent than the parent, unsubstituted DDACTHF, whereas 1 and 2 exhibited more modest growth inhibition activity (1, IC50 = 1.0 microM and 2, IC50 = 2.0 microM). 相似文献
100.