全文获取类型
收费全文 | 113篇 |
免费 | 5篇 |
出版年
2021年 | 1篇 |
2020年 | 1篇 |
2018年 | 3篇 |
2016年 | 1篇 |
2014年 | 4篇 |
2013年 | 3篇 |
2012年 | 5篇 |
2011年 | 9篇 |
2010年 | 3篇 |
2009年 | 3篇 |
2008年 | 5篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 5篇 |
2004年 | 3篇 |
2003年 | 2篇 |
2002年 | 4篇 |
2001年 | 2篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 4篇 |
1989年 | 1篇 |
1988年 | 5篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1964年 | 1篇 |
1953年 | 1篇 |
1941年 | 1篇 |
排序方式: 共有118条查询结果,搜索用时 703 毫秒
11.
Dobly A Martin SA Blaney SC Houlihan DF 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2004,137(1):75-85
The efficiency with which fish and other animals add and maintain body proteins is a balance between synthesis of proteins and their degradation. In fish that have similar food consumption and protein synthesis rates, a greater ratio of synthesis to degradation would be expected to produce more efficient conversion of food into growth. In addition, we hypothesised that high activities of the proteasome, a major pathway of protein degradation, would be negatively correlated with growth rate. In order to test this hypothesis we maintained rainbow trout for 62 days, during which repeat measurements of food consumption and growth were made. We selected fish for high and low growth efficiencies. Protein degradation was estimated from the difference between protein synthesis (determined by 15N flux) and protein growth. We found that protein synthesis rates were significantly higher in the low growth efficiency group, as were estimated protein degradation rates. In another group of fish that also did not differ in food consumption, the activity of the proteasome in the liver, but not in the muscle, was negatively correlated with growth rates. These two experiments showed that high proteasome activity is linked to decreased growth efficiency. 相似文献
12.
A live,attenuated dengue virus type 1 vaccine candidate with a 30-nucleotide deletion in the 3' untranslated region is highly attenuated and immunogenic in monkeys 总被引:1,自引:0,他引:1 下载免费PDF全文
Whitehead SS Falgout B Hanley KA Blaney Jr JE Markoff L Murphy BR 《Journal of virology》2003,77(2):1653-1657
The Delta30 deletion mutation, which was originally created in dengue virus type 4 (DEN4) by the removal of nucleotides 172 to 143 from the 3' untranslated region (3' UTR), was introduced into a homologous region of wild-type (wt) dengue virus type 1 (DEN1). The resulting virus, rDEN1Delta30, was attenuated in rhesus monkeys to a level similar to that of the rDEN4Delta30 vaccine candidate. rDEN1Delta30 was more attenuated in rhesus monkeys than the previously described vaccine candidate, rDEN1mutF, which also contains mutations in the 3' UTR, and both vaccines were highly protective against challenge with wt DEN1. Both rDEN1Delta30 and rDEN1mutF were also attenuated in HuH-7-SCID mice. However, neither rDEN1Delta30 nor rDEN1mutF showed restricted replication following intrathoracic inoculation in the mosquito Toxorhynchites splendens. The ability of the Delta30 mutation to attenuate both DEN1 and DEN4 viruses suggests that a tetravalent DEN vaccine could be generated by introduction of the Delta30 mutation into wt DEN viruses belonging to each of the four serotypes. 相似文献
13.
Toxicity and behavioural effects of diet-borne alkaloids on larvae of the black blowfly,Phormia regina 总被引:2,自引:0,他引:2
Larvae of the black blowfly, Phormia regina (Meigen) (Diptera: Calliphoridae) were exposed for 24 h to artificial diets that contained one of the following alkaloids: arecoline, caffeine, nicotine, quinine, sparteine or strychnine at either 1000 or 100 p.p.m. Each of the alkaloids caused reduced weight gain, relative to a control population in a no-choice bioassay and, with the exception of quinine, all alkaloids caused reduced larval weights in a choice bioassay. Larvae were unable to move away from diets containing arecoline (1000 and 100 p.p.m) and congregated away from diets containing 1000 p.p.m. quinine. Arecoline (1000 p.p.m) and both concentrations of nicotine caused significant mortality of larvae. Over a longer period (120 h), 10 and 1 p.p.m. nicotine resulted in significant numbers of larvae congregating away from a treated diet. Ten p.p.m. nicotine caused reduced weight gain over 120 h, although larvae provided with a choice were less affected. Exposure of larvae to dried residues of nicotine for 2 h did not affect subsequent development. 相似文献
14.
Dawson TJ Blaney CE Munn AJ Krockenberger A Maloney SK 《Physiological and biochemical zoology : PBZ》2000,73(3):374-381
We examined thermoregulation in red kangaroos (Macropus rufus) from deserts and in eastern grey kangaroos (Macropus giganteus) from mesic forests/woodlands. Desert kangaroos have complex evaporative heat loss mechanisms, but the relative importance of these mechanisms is unclear. Little is known of the abilities of grey kangaroos. Our detailed study of these kangaroos' thermoregulatory responses at air temperatures (T(a)) from -5 degrees to 45 degrees C showed that, while some differences occur, their abilities are fundamentally similar. Both species show the basic marsupial characteristics of relatively low basal metabolism and body temperature (T(b)). Within the thermoneutral zone, T(b) was 36.3 degrees + or - 0.1 degrees C (X + or - SE) in both species, and except for a small rise at T(a) 45 degrees C, T(b) was stable over a wide range of T(a). Metabolic heat production was 25% higher in red kangaroos at T(a) -5 degrees C. At the highest T(a) (45 degrees C), both species relied on evaporative heat loss (EHL) to maintain T(b); both panting and licking were used. The eastern grey kangaroo utilised panting (76% of EHL) as the principal mode of EHL, and while this was so for red kangaroos, cutaneous evaporative heat loss (CEHL) was significant (40% of EHL). CEHL appeared to be mainly licking, as evidenced from surface temperatures. Both species utilised peripheral vascular adjustments to control heat flow, as indicated by changes in dry conductance (C(dry)). At lower temperatures, C(dry) was minimal, but it increased significantly at T(a) just below T(b) (33 degrees C); in these conditions, the C(dry) of red kangaroos was significantly higher than that of eastern grey kangaroos, indicating a greater reliance on dry heat loss. Under conditions where heat flows into the body from the environment (T(a) 45 degrees C), there was peripheral vasoconstriction to reduce this inflow; C(dry) decreased significantly from the values seen at 33 degrees C in both kangaroos. The results indicated that, while both species have excellent thermoregulatory abilities, the desert red kangaroos may cope better with more extreme temperatures, given that they respond to T(a) 45 degrees C with lower respiratory evaporation than do the eastern grey kangaroos. 相似文献
15.
S.R. Belmain W.M. Blaney M.S.J. Simmonds 《Entomologia Experimentalis et Applicata》1998,89(2):193-199
In a choice bio-assay adult female deathwatch beetles were offered two dendrochronologically dated wood blocks from oak timber to study oviposition preference behaviour. There was a clear preference for ovipositing on old wood dating from the 13th to 19th centuries rather than new wood from the 20th century. Control, same-century choice, experiments showed that beetles will oviposit on young wood and that the age of the wood does not alter the overall oviposition potential. Oviposition frequency varied with insect age. Fecundity of insects collected from an infested building was similar to that of insects maintained in culture. 相似文献
16.
Lovell PJ Blaney FE Goodacre CJ Scott CM Smith PW Starr KR Thewlis KM Vong AK Ward SE Watson JM 《Bioorganic & medicinal chemistry letters》2007,17(4):1033-1036
Investigation of halogen substitution in lead compound 1 has led to the identification of analogues which combine high affinity for 5-HT(1A) receptors and potent serotonin reuptake inhibitory activity. Several compounds show an improved selectivity over 5-HT(1B) and 5-HT(1D) receptors and a superior pharmacokinetic profile in the rat. 相似文献
17.
Engelthaler DM Bowers J Schupp JA Pearson T Ginther J Hornstra HM Dale J Stewart T Sunenshine R Waddell V Levy C Gillece J Price LB Contente T Beckstrom-Sternberg SM Blaney DD Wagner DM Mayo M Currie BJ Keim P Tuanyok A 《PLoS neglected tropical diseases》2011,5(10):e1347
Melioidosis is caused by Burkholderia pseudomallei, a Gram-negative bacillus, primarily found in soils in Southeast Asia and northern Australia. A recent case of melioidosis in non-endemic Arizona was determined to be the result of locally acquired infection, as the patient had no travel history to endemic regions and no previous history of disease. Diagnosis of the case was confirmed through multiple microbiologic and molecular techniques. To enhance the epidemiological analysis, we conducted several molecular genotyping procedures, including multi-locus sequence typing, SNP-profiling, and whole genome sequence typing. Each technique has different molecular epidemiologic advantages, all of which provided evidence that the infecting strain was most similar to those found in Southeast Asia, possibly originating in, or around, Malaysia. Advancements in new typing technologies provide genotyping resolution not previously available to public health investigators, allowing for more accurate source identification. 相似文献
18.
Blaney Davidson EN Scharstuhl A Vitters EL van der Kraan PM van den Berg WB 《Arthritis research & therapy》2005,7(6):R1338-R1347
Osteoarthritis (OA) is a common joint disease, mainly effecting the elderly population. The cause of OA seems to be an imbalance
in catabolic and anabolic factors that develops with age. IL-1 is a catabolic factor known to induce cartilage damage, and
transforming growth factor (TGF)-beta is an anabolic factor that can counteract many IL-1-induced effects. In old mice, we
observed reduced responsiveness to TGF-beta-induced IL-1 counteraction. We investigated whether expression of TGF-beta and
its signaling molecules altered with age. To mimic the TGF-beta deprived conditions in aged mice, we assessed the functional
consequence of TGF-beta blocking. We isolated knee joints of mice aged 5 months or 2 years, half of which were exposed to
IL-1 by intra-articular injection 24 h prior to knee joint isolation. Immunohistochemistry was performed, staining for TGF-beta1,
-2 or -3, TGF-betaRI or -RII, Smad2, -3, -4, -6 and -7 and Smad-2P. The percentage of cells staining positive was determined
in tibial cartilage. To mimic the lack of TGF-beta signaling in old mice, young mice were injected with IL-1 and after 2 days
Ad-LAP (TGF-beta inhibitor) or a control virus were injected. Proteoglycan (PG) synthesis (35S-sulfate incorporation) and PG content of the cartilage were determined. Our experiments revealed that TGF-beta2 and -3 expression
decreased with age, as did the TGF-beta receptors. Although the number of cells positive for the Smad proteins was not altered,
the number of cells expressing Smad2P strongly dropped in old mice. IL-1 did not alter the expression patterns. We mimicked
the lack of TGF-beta signaling in old mice by TGF-beta inhibition with LAP. This resulted in a reduced level of PG synthesis
and aggravation of PG depletion. The limited response of old mice to TGF-beta induced-IL-1 counteraction is not due to a diminished
level of intracellular signaling molecules or an upregulation of intracellular inhibitors, but is likely due to an intrinsic
absence of sufficient TGF-beta receptor expression. Blocking TGF-beta distorted the natural repair response after IL-1 injection.
In conclusion, TGF-beta appears to play an important role in repair of cartilage and a lack of TGF-beta responsiveness in
old mice might be at the root of OA development. 相似文献
19.
Esmeralda N Blaney Davidson Elly L Vitters Wim B van den Berg Peter M van der Kraan 《Arthritis research & therapy》2006,8(3):R65-8
Cartilage damage in osteoarthritis (OA) is considered an imbalance between catabolic and anabolic factors, favoring the catabolic
side. We assessed whether adenoviral overexpression of transforming growth factor-β (TGFβ) enhanced cartilage repair and whether
TGFβ-induced fibrosis was blocked by local expression of the intracellular TGFβ inhibitor Smad7. We inflicted cartilage damage
by injection of interleukin-1 (IL-1) into murine knee joints. After 2 days, we injected an adenovirus encoding TGFβ. On day
4, we measured proteoglycan (PG) synthesis and content. To examine whether we could block TGFβ-induced fibrosis and stimulate
cartilage repair simultaneously, we injected Ad-TGFβ and Ad-Smad7. This was performed both after IL-1-induced damage and in
a model of primary OA. In addition to PG in cartilage, synovial fibrosis was measured by determining the synovial width and
the number of procollagen I-expressing cells. Adenoviral overexpression of TGFβ restored the IL-1-induced reduction in PG
content and increased PG synthesis. TGFβ-induced an elevation in PG content in cartilage of the OA model. TGFβ-induced synovial
fibrosis was strongly diminished by simultaneous synovial overexpression of Smad7 in the synovial lining. Of great interest,
overexpression of Smad7 did not reduce the repair-stimulating effect of TGFβ on cartilage. Adenoviral overexpression of TGFβ
stimulated repair of IL-1- and OA-damaged cartilage. TGFβ-induced synovial fibrosis was blocked by locally inhibiting TGFβ
signaling in the synovial lining by simultaneously transfecting it with an adenovirus overexpressing Smad7. 相似文献
20.
van der Kraan PM Goumans MJ Blaney Davidson E ten Dijke P 《Cell and tissue research》2012,347(1):257-265
Osteoarthritis (OA) is a disease of articular cartilage, with aging as the main risk factor. In OA, changes in chondrocytes
lead to the autolytic destruction of cartilage. Transforming growth factor-β has recently been demonstrated to signal not
only via activin receptor-like kinase 5 (ALK5)-induced Smad2/3 phosphorylation, but also via ALK1-induced Smad1/5/8 phosphorylation
in articular cartilage. In aging cartilage and experimental OA, the ratio ALK1/ALK5 has been found to be increased, and the
expression of ALK1 is correlated with matrix metalloproteinase-13 expression. The age-dependent shift towards Smad1/5/8 signalling
might trigger the differentiation of articular chondrocytes with an autolytic phenotype. 相似文献