全文获取类型
收费全文 | 204篇 |
免费 | 21篇 |
国内免费 | 1篇 |
出版年
2022年 | 1篇 |
2021年 | 7篇 |
2020年 | 2篇 |
2019年 | 4篇 |
2018年 | 3篇 |
2017年 | 7篇 |
2016年 | 9篇 |
2015年 | 6篇 |
2014年 | 8篇 |
2013年 | 10篇 |
2012年 | 13篇 |
2011年 | 9篇 |
2010年 | 15篇 |
2009年 | 11篇 |
2008年 | 14篇 |
2007年 | 10篇 |
2006年 | 5篇 |
2005年 | 7篇 |
2004年 | 3篇 |
2003年 | 8篇 |
2002年 | 7篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 12篇 |
1997年 | 7篇 |
1996年 | 6篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 6篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1987年 | 3篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
排序方式: 共有226条查询结果,搜索用时 342 毫秒
61.
62.
Stoats are significant predators of native fauna in New Zealand. They occur in many habitat types and consume a wide range of prey. The diet of stoats in the Tasman River, South Canterbury, was studied by analysis of scats and den contents. Analysis of 206 scats showed that stoats ate mainly lagomorphs, birds and invertebrates. Minor components included mice, lizards, fish and hedgehogs. Stoats ate more birds in spring than in autumn, and female stoats ate more invertebrates than did males. The contents of 219 dens collected in the same area at the same time provided further information. Birds and lagomorphs occurred at high frequency in dens, and other components were minor. Remains in dens were larger than in scats and allowed identification of many more prey items to species level. Den contents revealed a potentially substantial impact of stoats on threatened shorebirds locally; this impact was not detected by analysis of scats. 相似文献
63.
Dong Eun Kim Martijn E. T. Doll Wilbert P. Vermeij Akos Gyenis Katharina Vogel Jan H. J. Hoeijmakers Christopher D. Wiley Albert R. Davalos Paul Hasty Pierre‐Yves Desprez Judith Campisi 《Aging cell》2020,19(3)
ERCC1 (excision repair cross complementing‐group 1) is a mammalian endonuclease that incises the damaged strand of DNA during nucleotide excision repair and interstrand cross‐link repair. Ercc1?/Δ mice, carrying one null and one hypomorphic Ercc1 allele, have been widely used to study aging due to accelerated aging phenotypes in numerous organs and their shortened lifespan. Ercc1?/Δ mice display combined features of human progeroid and cancer‐prone syndromes. Although several studies report cellular senescence and apoptosis associated with the premature aging of Ercc1?/Δ mice, the link between these two processes and their physiological relevance in the phenotypes of Ercc1?/Δ mice are incompletely understood. Here, we show that ERCC1 depletion, both in cultured human fibroblasts and the skin of Ercc1?/Δ mice, initially induces cellular senescence and, importantly, increased expression of several SASP (senescence‐associated secretory phenotype) factors. Cellular senescence induced by ERCC1 deficiency was dependent on activity of the p53 tumor‐suppressor protein. In turn, TNFα secreted by senescent cells induced apoptosis, not only in neighboring ERCC1‐deficient nonsenescent cells, but also cell autonomously in the senescent cells themselves. In addition, expression of the stem cell markers p63 and Lgr6 was significantly decreased in Ercc1?/Δ mouse skin, where the apoptotic cells are localized, compared to age‐matched wild‐type skin, possibly due to the apoptosis of stem cells. These data suggest that ERCC1‐depleted cells become susceptible to apoptosis via TNFα secreted from neighboring senescent cells. We speculate that parts of the premature aging phenotypes and shortened health‐ or lifespan may be due to stem cell depletion through apoptosis promoted by senescent cells. 相似文献
64.
Ben T. van den Brand Eline A. Vermeij Claire E. J. Waterborg Onno J. Arntz Michael Kracht Miranda B. Bennink Wim B. van den Berg Fons A. J. van de Loo 《PloS one》2013,8(2)
Antigen presenting cells (APCs) play an important role in arthritis and APC specific gene therapeutic targeting will enable intracellular modulation of cell activity. Viral mediated overexpression is a potent approach to achieve adequate transgene expression levels and lentivirus (LV) is useful for sustained expression in target cells. Therefore, we studied the feasibility of lentiviral mediated targeting of APCs in experimental arthritis. Third generation VSV-G pseudotyped self-inactivating (SIN)-LV were injected intravenously and spleen cells were analyzed with flow cytometry for green fluorescent protein (GFP) transgene expression and cell surface markers. Collagen-induced arthritis (CIA) was induced by immunization with bovine collagen type II in complete Freund''s adjuvant. Effect on inflammation was monitored macroscopically and T-cell subsets in spleen were analyzed by flow cytometry. Synovium from arthritic knee joints were analyzed for proinflammatory cytokine expression. Lentiviruses injected via the tail vein preferentially infected the spleen and transduction peaks at day 10. A dose escalating study showed that 8% of all spleen cells were targeted and further analysis showed that predominantly Ly6C+ and F4/80+ cells in spleen were targeted by the LV. To study the feasibility of blocking TAK1-dependent pathways by this approach, a catalytically inactive mutant of TAK1 (TAK1-K63W) was overexpressed during CIA. LV-TAK1-K63W significantly reduced incidence and arthritis severity macroscopically. Further histological analysis showed a significant decrease in bone erosion in LV-TAK1-K63W treated animals. Moreover, systemic Th17 levels were decreased by LV-TAK1-K63W treatment in addition to diminished IL-6 and KC production in inflamed synovium. In conclusion, systemically delivered LV efficiently targets monocytes and macrophages in spleen that are involved in autoimmune arthritis. Moreover, this study confirms efficacy of TAK1 targeting in arthritis. This approach may provide a valuable tool in targeting splenic APCs, to unravel their role in autoimmune arthritis and to identify and validate APC specific therapeutic targets. 相似文献
65.
Geerat J. Vermeij 《Palaeontology》2020,63(6):1035-1047
As animals grow in size, their relationship to the physical environment necessarily changes, but molluscs and brachiopods whose accretionary skeletons expand at one end of a hollow cone conform to logarithmic-spiral growth and retain a constant shape. Dissolution and remodelling of previously formed parts of the skeleton can alleviate the constraints of strict logarithmic-spiral growth. How, when, where and in which clades mineral skeletal resorption has evolved are important questions because they relate to the conditions and history of skeletal formation and to the way in which ocean acidification in the past influenced that history. A synthesis of data on mineral dissolution in shells shows that resorption from the inner surface of bivalve shells occurs under temporarily anaerobic conditions within the closed shell, but functional remodelling is unknown in bivalves. Resorption and functional remodelling occur in brachiopods, gastropods and terrestrial hermit crabs, and to a lesser extent in scaphopods and cephalopods. Internal whorl resorption leading to a more compact visceral mass has evolved at least ten times in gastropods. Contrary to expectations stemming from patterns in the availability of calcium, gastropod remodelling is a phenomenon of warm, calcium-rich environments and not of cold acidified conditions. There is therefore no evidence that internal whorl resorption increases calcium-use efficiency. Resorption is one of several mechanisms that have enabled animal skeletons to become more dynamic and adaptable during ontogeny. 相似文献
66.
Cyanine dye-protein interactions: looking for fluorescent probes for amyloid structures 总被引:1,自引:0,他引:1
Volkova KD Kovalska VB Balanda AO Vermeij RJ Subramaniam V Slominskii YL Yarmoluk SM 《Journal of biochemical and biophysical methods》2007,70(5):727-733
We ascertained the ability to detect fibrillar beta-lactoglobulin (BLG) of a series of mono-, tri-, penta-, and heptamethinecyanines based on benzothiazole and benzimidazole heterocycles, and of benzothiazole squaraine. Fluorescence properties of these cyanine dyes were measured in the unbound state and in the presence of monomeric and fibrillar BLG and compared with those for the commercially available benzothiazole dye Thioflavin T. The correlation between the chemical nature of the dye molecules and the ability of dyes to bind aggregated proteins was established. We found that meso-substituted cyanines with amino substituents in heterocycle in contrast to the corresponding unsubstituted dyes have a binding preference to fibrillar BLG and a noticeable fluorescence response in the presence of the aggregated protein. For the squaraines and benzimidazole penthamethinecyanines studied, fluorescence emission increased both in the presence of native and fibrillar protein. The trimethinecyanines T-49 and SH-516 exhibit specifically increased fluorescence in the presence of fibrillar BLG. These dyes demonstrated the same or higher emission intensity and selectivity to aggregated BLG as Thioflavin T, and are proposed for application in selective fluorescent detection of aggregated proteins. 相似文献
67.
Egbert G. Leigh Aaron O'Dea Geerat J. Vermeij 《Biological reviews of the Cambridge Philosophical Society》2014,89(1):148-172
About 3 million years ago (Ma), the Isthmus of Panama joined the Americas, forming a land bridge over which inhabitants of each America invaded the other—the Great American Biotic Interchange. These invasions transformed land ecosystems in South and Middle America. Humans invading from Asia over 12000 years ago killed most mammals over 44 kg, again transforming tropical American ecosystems. As a sea barrier, the isthmus induced divergent environmental change off its two coasts—creating contrasting ecosystems through differential extinction and diversification. Approximately 65 Ma invading marsupials and ungulates of North American ancestry, and xenarthrans of uncertain provenance replaced nearly all South America's non‐volant mammals. There is no geological evidence for a land bridge at that time. Together with rodents and primates crossing from Africa 42 to 30 Ma, South America's mammals evolved in isolation until the interchange's first heralds less than 10 Ma. Its carnivores were ineffective marsupials. Meanwhile, North America was invaded by more competitive Eurasian mammals. The Americas had comparable expanses of tropical forest 55 Ma; later, climate change confined North American tropical forest to a far smaller area. When the isthmus formed, North American carnivores replaced their marsupial counterparts. Although invaders crossed in both directions, North American mammals spread widely, diversified greatly, and steadily replaced South American open‐country counterparts, unused to effective predators. Invading South American mammals were less successful. South America's birds, bats, and smaller rainforest mammals, equally isolated, mostly survived invasion. Its vegetation, enriched by many overseas invaders, remained intact. This vegetation resists herbivory effectively. When climate permitted, South America's rainforest, with its bats, birds and mammals, spread to Mexico. Present‐day tropical American vegetation is largely zoned by trade‐offs between exploiting well‐watered settings versus surviving droughts, exploiting fertile versus coping with poor soil, and exploiting lowland warmth versus coping with cooler altitudes. At the start of the Miocene, a common marine biota extended from Trinidad to Ecuador and western Mexico, which evolved in isolation from the Indo‐Pacific until the Pleistocene. The seaway between the Americas began shoaling over 12 Ma. About 10 Ma the land bridge was briefly near‐complete, allowing some interchange of land mammals between the continents. By 7 Ma, the rising sill had split deeper‐water populations. Sea temperature, salinity and sedimentary carbon content had begun to increase in the Southern Caribbean, but not the Pacific. By 4 Ma, the seaway's narrowing began to extinguish Caribbean upwellings. By 2 Ma, upwellings remained only along Venezuela; Caribbean plankton, suspension‐feeding molluscs and their predators had declined sharply, largely replaced by bottom‐dwelling corals and calcareous algae and magnificent coral reefs. Closing the seaway extinguished the Eastern Pacific's reef corals (successors recolonized from the Indo‐Pacific 6000 years ago), whereas many molluscs of productive waters that once thrived in the Caribbean now survive only in the Eastern Pacific. The present‐day productive Eastern Pacific, with few, small coral reefs and a plankton‐based ecosystem contrasts with the Caribbean, whose clear water favours expansive coral reefs and bottom‐dwelling primary producers. These ecosystems reflect the trade‐off between fast growth and effective defence with attendant longevity. Overfishing with new technologies during the last few centuries, however, has caused population crashes of ever‐smaller marine animals, devastating Caribbean ecosystems. 相似文献
68.
T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?
Zana Brkic Odilia BJ Corneth Cornelia G van Helden-Meeuwsen Radboud JEM Dolhain Naomi I Maria Sandra MJ Paulissen Nadine Davelaar Jan Piet van Hamburg Paul L van Daele Virgil A Dalm P Martin van Hagen Johanna MW Hazes Marjan A Versnel Erik Lubberts 《Arthritis research & therapy》2014,16(2):R62
Introduction
A hallmark of systemic autoimmune diseases like systemic lupus erythematosus (SLE) is the increased expression of interferon (IFN) type I inducible genes, so-called IFN type I signature. Recently, T-helper 17 subset (Th17 cells), which produces IL-17A, IL-17F, IL-21, and IL-22, has been implicated in SLE. As CCR6 enriches for Th17 cells, we used this approach to investigate whether CCR6+ memory T-helper cells producing IL-17A, IL-17F, IL-21, and/or IL-22 are increased in SLE patients and whether this increase is related to the presence of IFN type I signature.Methods
In total, 25 SLE patients and 15 healthy controls (HCs) were included. SLE patients were divided into IFN type I signature-positive (IFN+) (n = 16) and negative (IFN-) (n = 9) patients, as assessed by mRNA expression of IFN-inducible genes (IFIGs) in monocytes. Expression of IL-17A, IL-17F, IL-21, and IL-22 by CD4+CD45RO+CCR6+ T cells (CCR6+ cells) was measured with flow cytometry and compared between IFN+, IFN- patients and HCs.Results
Increased percentages of IL-17A and IL-17A/IL-17F double-producing CCR6+ cells were observed in IFN+ patients compared with IFN- patients and HCs. IL-17A and IL-17F expression within CCR6+ cells correlated significantly with IFIG expression. In addition, we found significant correlation between B-cell activating factor of the tumor necrosis family (BAFF)–a factor strongly correlating with IFN type I - and IL-21 producing CCR6+ cells.Conclusions
We show for the first time higher percentages of IL-17A and IL-17A/IL-17F double-producing CCR6+ memory T-helper cells in IFN+ SLE patients, supporting the hypothesis that IFN type I co-acts with Th17 cytokines in SLE pathogenesis. 相似文献69.
Kai Yu Zhang Angela E Kedgley Claire R Donoghue Daniel Rueckert Anthony MJ Bull 《Arthritis research & therapy》2014,16(1):R27
Introduction
The meniscus has an important role in force transmission across the knee, but a detailed three-dimensional (3D) morphometric shape analysis of the lateral meniscus to elucidate subject-specific function has not been conducted. The aim of this study was to perform 3D morphometric analyses of the lateral meniscus in order to correlate shape variables with anthropometric parameters, thereby gaining a better understanding of the relationship between lateral meniscus shape and its load-bearing function.Methods
The lateral meniscus (LM) was manually segmented from magnetic resonance images randomly selected from the Osteoarthritis Initiative (OAI) non-exposed control subcohort. A 3D statistical shape model (SSM) was constructed to extract the principal morphological variations (PMV) of the lateral meniscus for 50 subjects (25 male and 25 female). Correlations between the principal morphological variations and anthropometric parameters were tested. Anthropometric parameters that were selected included height, weight, body mass index (BMI), femoral condyle width and axial rotation.Results
The first principal morphological variation (PMV) was found to correlate with height (r = 0.569), weight (r = 0.647), BMI (r = 0.376), and femoral condyle width (r = 0.622). The third PMV was found to correlate with height (r = 0.406), weight (r = 0.312), and femoral condyle width (r = 0.331). The percentage of the tibial plateau covered by the lateral meniscus decreases as anthropometric parameters relating to size of the subject increase. Furthermore, when the size of the subject increases, the posterior and anterior horns become proportionally longer and wider.Conclusion
The correlations discovered suggest that variations in meniscal shape can be at least partially explained by the levels of loads transmitted across the knee on a regular basis. Additionally, as the size of the subject increases and body weight rises, the coverage percentage of the meniscus is reduced, suggesting that there would be an increase in the load-bearing by the cartilage. However, this reduced coverage percentage is compensated by the proportionally wider and longer meniscal horn. 相似文献70.
MJ Müller MP Mendon?a IR Oliveira LPL de Oliveira VLS Valente VH Valiati 《Neotropical Entomology》2012,41(2):112-120
We describe for the first time the sexual behavior and the courtship song of males of the African fly Zaprionus indianus (Gupta), a recent invader of South America. The male courtship song is formed by monocyclic pulses and the courtship behavior is simple when compared to that of species of Drosophila. Two interpulse interval (IPI) distributions were observed: pre-mounting and mounting. No significant difference was observed between the pre-mounting IPIs of males that descended from three geographical populations from South America. We also observed the songs produced by females and the homosexual behavior exhibited by males. A sequence of bursts is produced by females as a refusal signal against males, while males emit a characteristic song that identifies sex genus, which differs from the courtship song. The short courtship and mating latencies recorded reveal vigorous males and receptive females, respectively. 相似文献