全文获取类型
收费全文 | 79篇 |
免费 | 15篇 |
出版年
2021年 | 1篇 |
2016年 | 1篇 |
2015年 | 2篇 |
2014年 | 3篇 |
2013年 | 3篇 |
2012年 | 2篇 |
2011年 | 9篇 |
2010年 | 5篇 |
2009年 | 3篇 |
2008年 | 5篇 |
2007年 | 3篇 |
2006年 | 8篇 |
2005年 | 3篇 |
2004年 | 7篇 |
2003年 | 4篇 |
2002年 | 1篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有94条查询结果,搜索用时 31 毫秒
1.
Construction of a mobilizable Yersinia enterocolitica virulence plasmid 总被引:27,自引:1,他引:26
Virulence of Yersinia enterocolitica O:8 is associated with pO:8, a 42-megadalton plasmid. We constructed a mobilizable pO:8 derivative by successive in vitro and in vivo genetic manipulations. The in vitro constructed hybrid molecule pRK290B8-5 consisting of the mobilizable vector pRK290B and a 2.9-megadalton BamHI fragment of pO:8 was conjugally transferred to a Y. enterocolitica strain of serotype O:8 which harbored the virulence plasmid pO:8. From Yersinia transconjugants, a cointegrate was isolated which apparently formed by homologous recombination between the two component plasmids. The cointegrate was mobilized into plasmidless Y. enterocolitica strains of different serotypes. The transconjugants of serotype O:8 were found to express all four plasmid-associated phenotypes: (i) mouse lethality (Ml), (ii) conjunctivitis provocation in the guinea pig eye (Con), (iii) calcium requirement for growth at 37 degrees C (Mox), and (iv) agglutinogens (Ag8). The transconjugants of serotype O:3 expressed the phenotypes Con, Mox, and Ag8 but were nonlethal for mice (Ml-). The transconjugants of serotype O:5 remained avirulent for mice (Ml-) and for the guinea pig eye (Con-) but expressed the phenotypes Mox and Ag8. These data show that the virulence plasmid is probably not functionally interchangeable within different serotypes of Y. enterocolitica. 相似文献
2.
The Haemophilus influenzae R plasmids specifying resistance against one, two, or three antibiotics which have emerged in different parts of the world were shown to have closely related but not identical plasmid cores. The gene for ampicillin resistance in the H. influenzae plasmid pKRE5367 is part of a transposon similar to Tn3, which was transposed from pKRE5367 onto RSF1010 in Escherichia coli. An indigenous H. influenzae plasmid (pW266) was isolated. Its properties correspond to those of the H. influenzae R plasmids, except for the presence of a drug resistance transposon. The in vitro-generated H. influenzae R plasmids carrying an ampicillin resistance transposon, a tetracycline resistance transposon, and a transposon for combined tetracycline-chloramphenicol resistance resembled the natural isolates. The findings support the hypothesis that the R plasmids of H. influenzae are of multiclonal evolutionary origin. 相似文献
3.
Kyrill S. Rogacev Gunnar H. Heine Günther Silbernagel Marcus E. Kleber Sarah Seiler Insa Emrich Simone Lennartz Christian Werner Adam M. Zawada Danilo Fliser Michael B?hm Winfried M?rz Hubert Scharnagl Ulrich Laufs 《PloS one》2016,11(1)
Background
Impaired renal function causes dyslipidemia that contributes to elevated cardiovascular risk in patients with chronic kidney disease (CKD). The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of the LDL receptor and plasma cholesterol concentrations. Its relationship to kidney function and cardiovascular events in patients with reduced glomerular filtration rate (GFR) has not been explored.Methods
Lipid parameters including PCSK9 were measured in two independent cohorts. CARE FOR HOMe (Cardiovascular and Renal Outcome in CKD 2–4 Patients—The Forth Homburg evaluation) enrolled 443 patients with reduced GFR (between 90 and 15 ml/min/1.73 m2) referred for nephrological care that were prospectively followed for the occurrence of a composite cardiovascular endpoint. As a replication cohort, PCSK9 was quantitated in 1450 patients with GFR between 90 and 15 ml/min/1.73 m2 enrolled in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC) that were prospectively followed for cardiovascular deaths.Results
PCSK9 concentrations did not correlate with baseline GFR (CARE FOR HOMe: r = -0.034; p = 0.479; LURIC: r = -0.017; p = 0.512). 91 patients in CARE FOR HOMe and 335 patients in LURIC reached an endpoint during a median follow-up of 3.0 [1.8–4.1] years and 10.0 [7.3–10.6] years, respectively. Kaplan-Meier analyses showed that PCSK9 concentrations did not predict cardiovascular events in either cohort [CARE FOR HOMe (p = 0.622); LURIC (p = 0.729)]. Sensitivity analyses according to statin intake yielded similar results.Conclusion
In two well characterized independent cohort studies, PCSK9 plasma levels did not correlate with kidney function. Furthermore, PCSK9 plasma concentrations were not associated with cardiovascular events in patients with reduced renal function. 相似文献4.
Inflammatory cytokines and oxidized low density lipoproteins increase endothelial cell expression of membrane type 1-matrix metalloproteinase 总被引:9,自引:0,他引:9
Rajavashisth TB Liao JK Galis ZS Tripathi S Laufs U Tripathi J Chai NN Xu XP Jovinge S Shah PK Libby P 《The Journal of biological chemistry》1999,274(17):11924-11929
5.
6.
In vivo analysis of cell division, cell growth, and differentiation at the shoot apical meristem in Arabidopsis 总被引:5,自引:0,他引:5 下载免费PDF全文
The aerial parts of the plant are generated by groups of rapidly dividing cells called shoot apical meristems. To analyze cell behavior in these structures, we developed a technique to visualize living shoot apical meristems using the confocal microscope. This method, combined with green fluorescent protein marker lines and vital stains, allows us to follow the dynamics of cell proliferation, cell expansion, and cell differentiation at the shoot apex. Using this approach, the effects of several mitotic drugs on meristem development were studied. Oryzalin (depolymerizing microtubules) very rapidly caused cell division arrest. Nevertheless, both cell expansion and cell differentiation proceeded in the treated meristems. Interestingly, DNA synthesis was not blocked, and the meristematic cells went through several rounds of endoreduplication in the presence of the drug. We next treated the meristems with two inhibitors of DNA synthesis, aphidicolin and hydroxyurea. In this case, cell growth and, later, cell differentiation were inhibited, suggesting an important role for DNA synthesis in growth and patterning. 相似文献
7.
How does the eye breathe? Evidence for neuroglobin-mediated oxygen supply in the mammalian retina 总被引:29,自引:0,他引:29
Schmidt M Giessl A Laufs T Hankeln T Wolfrum U Burmester T 《The Journal of biological chemistry》2003,278(3):1932-1935
Visual performance of the vertebrate eye requires large amounts of oxygen, and thus the retina is one of the highest oxygen-consuming tissues of the body. Here we show that neuroglobin, a neuron-specific respiratory protein distantly related to hemoglobin and myoglobin, is present at high amounts in the mouse retina (approximately 100 microm). The estimated concentration of neuroglobin in the retina is thus about 100-fold higher than in the brain and is in the same range as that of myoglobin in the muscle. Neuroglobin is expressed in all neurons of the retina but not in the retinal pigment epithelium. Neuroglobin mRNA was detected in the perikarya of the nuclear and ganglion layers of the neuronal retina, whereas the protein was present mainly in the plexiform layers and in the ellipsoid region of photoreceptor inner segment. The distribution of neuroglobin correlates with the subcellular localization of mitochondria and with the relative oxygen demands, as the plexiform layers and the inner segment consume most of the retinal oxygen. These findings suggest that neuroglobin supplies oxygen to the retina, similar to myoglobin in the myocardium and the skeletal muscle. 相似文献
8.
Vernoux T Kronenberger J Grandjean O Laufs P Traas J 《Development (Cambridge, England)》2000,127(23):5157-5165
The process of organ positioning has been addressed, using the pin-formed 1 (pin1) mutant as a tool. PIN1 is a transmembrane protein involved in auxin transport in Arabidopsis. Loss of function severely affects organ initiation, and pin1 mutants are characterised by an inflorescence meristem that does not initiate any flowers, resulting in the formation of a naked inflorescence stem. This phenotype, combined with the proposed role of PIN1 in hormone transport, makes the mutant an ideal tool to study organ formation and phyllotaxis, and here we present a detailed analysis of the molecular modifications at the shoot apex caused by the mutation. We show that meristem structure and function are not severely affected in the mutant. Major alterations, however, are observed at the periphery of the pin1 meristem, where organ initiation should occur. Although two very early markers of organ initiation, LEAFY and AINTEGUMENTA, are expressed at the periphery of the mutant meristem, the cells are not recruited into distinct primordia. Instead a ring-like domain expressing those primordium specific genes is observed around the meristem. This ring-like domain also expresses a boundary marker, CUP-SHAPED COTYLEDON 2, involved in organ separation, showing that the zone at the meristem periphery has a hybrid identity. This implies that PIN1 is not only involved in organ outgrowth, but that it is also necessary for organ separation and positioning. A model is presented in which PIN1 and the local distribution of auxin control phyllotaxis. 相似文献
9.
Marlon R. Veldwijk Leopold Sellner Marius Stiefelhagen Jürgen A. Kleinschmidt Stephanie Laufs Julian Topaly Stefan Fruehauf W. Jens Zeller Frederik Wenz 《Cytotherapy》2010,12(1):107-112
Background and aimsBecause of their pluripotency, human CD34+ peripheral blood progenitor cells (PBPC) are targets of interest for the treatment of many acquired and inherited disorders using gene therapeutic approaches. Unfortunately, most current vector systems lack either sufficient transduction efficiency or an appropriate safety profile. Standard single-stranded recombinant adeno-associated virus 2 (AAV2)-based vectors offer an advantageous safety profile, yet lack the required efficiency in human PBPC.MethodsA panel of pseudotyped AAV vectors (designated AAV2/x, containing the vector genome of serotype 2 and capsid of serotype x, AAV2/1–AAV2/6) was screened on primary human granulocyte–colony-stimulating factor (G-CSF)-mobilized CD34+ PBPC to determine their gene transfer efficacy. Additionally, double-stranded self-complementary AAV (dsAAV) were used to determine possible second-strand synthesis limitations.ResultsAAV2/6 vectors proved to be the most efficient [12.8% (1.8–25.4%) transgene-expressing PBPC after a single transduction], being significantly more efficient (all P < 0.005) than the other vectors [AAV2/2, 2.0% (0.2–7.3%); AAV2/1, 1.3% (0.1–2.9%); others, <; 1% transgene-expressing PBPC]. In addition, the relevance of the single-to-double-strand conversion block in transduction of human PBPC could be shown using pseudotyped dsAAV vectors: for dsAAV2/2 [9.3% (8.3–20.3%); P < 0.001] and dsAAV2/6 [37.7% (23.6–61.0%); P < 0.001) significantly more PBPC expressed the transgene compared with their single-stranded counterparts; for dsAAV2/1, no significant increase could be observed.ConclusionsWe have shown that clinically relevant transduction efficiency levels using AAV-based vectors in human CD34+ PBPC are feasible, thereby offering an efficient alternative vector system for gene transfer into this important target cell population. 相似文献