全文获取类型
收费全文 | 401篇 |
免费 | 23篇 |
专业分类
424篇 |
出版年
2023年 | 2篇 |
2022年 | 8篇 |
2021年 | 6篇 |
2020年 | 1篇 |
2019年 | 6篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 7篇 |
2015年 | 14篇 |
2014年 | 28篇 |
2013年 | 34篇 |
2012年 | 36篇 |
2011年 | 43篇 |
2010年 | 20篇 |
2009年 | 13篇 |
2008年 | 29篇 |
2007年 | 31篇 |
2006年 | 33篇 |
2005年 | 23篇 |
2004年 | 18篇 |
2003年 | 16篇 |
2002年 | 16篇 |
2000年 | 1篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1994年 | 2篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1974年 | 1篇 |
1950年 | 2篇 |
排序方式: 共有424条查询结果,搜索用时 12 毫秒
31.
32.
This study seeks to understand children''s perceptions of their present and future environments in the highly biodiverse and rapidly changing landscapes of Kalimantan, Indonesian Borneo. We analyzed drawings by children (target age 10–15 years) from 22 villages, which show how children perceive the present conditions of forests and wildlife surrounding their villages and how they expect conditions to change over the next 15 years. Analyses of picture elements and their relationships to current landscape variables indicate that children have a sophisticated understanding of their environment and how different environmental factors interact, either positively or negatively. Children appear to have landscape-dependent environmental perceptions, showing awareness of past environmental conditions and many aspects of recent trends, and translating these into predictions for future environmental conditions. The further removed their present landscape is from the originally forested one, the more environmental change they expect in the future, particularly declines in forest cover, rivers, animal diversity and increases in temperature and natural disasters. This suggests that loss of past perceptions and associated “shifting environmental baselines” do not feature strongly among children on Borneo, at least not for the perceptions we investigated here. Our findings that children have negative expectations of their future environmental conditions have important political implications. More than other generations, children have a stake in ensuring that future environmental conditions support their long-term well-being. Understanding what drives environmental views among children, and how they consider trade-offs between economic development and social and environmental change, should inform optimal policies on land use. Our study illuminates part of the complex interplay between perceptions of land cover and land use change. Capturing the views of children through artistic expressions provides a potentially powerful tool to influence public and political opinions, as well as a valuable approach for developing localized education and nature conservation programs. 相似文献
33.
Anne-Sophie Yribarren Daniel Thomas Alain Friboulet Bérangère Avalle 《European journal of biochemistry》2003,270(13):2789-2795
A library of random peptide sequences was used to select peptides that inhibit an anti-idiotypic catalytic Ig, immunoglobulin (IgG) 9G4H9, with a beta-lactamase-like activity. This library displays cyclic heptapeptides on the surface of bacteriophages and represents a collection of up to 4.5 x 109 peptides. The first selection step aimed at enriching the library in species that bind to the whole Ig molecule. The second step was to discriminate peptides that bind to part of the molecule other than the active site. Selected peptides were then screened by surface plasmon resonance analysis. Those displaying measurable Kd values were assayed for their ability to inhibit the catalytic Ig. 相似文献
34.
Elisabeth Lobner Anne-Sophie Humm Georg Mlynek Konstantin Kubinger Michael Kitzmüller Michael W. Traxlmayr 《MABS-AUSTIN》2017,9(7):1088-1104
Fcabs (Fc domain with antigen-binding sites) are promising novel therapeutics. By engineering of the C-terminal loops of the CH3 domains, 2 antigen binding sites can be inserted in close proximity. To elucidate the binding mode(s) between homodimeric Fcabs and small homodimeric antigens, the interaction between the Fcabs 448 and CT6 (having the AB, CD and EF loops and the C-termini engineered) with homodimeric VEGF was investigated. The crystal structures of these Fcabs, which form polymers with the antigen VEGF in solution, were determined. However, construction of heterodimeric Fcabs (JanusFcabs: one chain Fc-wt, one chain VEGF-binding) results in formation of distinct JanusFcab–VEGF complexes (2:1), which allowed elucidation of the crystal structure of the JanusCT6–VEGF complex at 2.15 Å resolution. VEGF binding to Janus448 and JanusCT6 is shown to be entropically unfavorable, but enthalpically favorable. Structure-function relationships are discussed with respect to Fcab design and engineering strategies. 相似文献
35.
The shell morphology of zebra mussels, Dreissena polymorpha, was analyzed to determine if alterations in shell shape and asymmetry between valves were related to its infection status, i.e. infected or not by microparasites like ciliates Ophryoglena spp. or intracellular bacteria Rickettsiales-like organisms (RLOs), and by macroparasites like trematodes Phyllodistomum folium and Bucephalus polymorphus. For microparasites, two groups of mussels were observed depending on shell measurements. Mussels with the more concave shells were the most parasitized by ciliates. This could be more a consequence than a cause and we hypothesized that a modification of the water flow through the mantle cavity could promote the infection with a ciliate. There were more RLOs present in the most symmetrical individuals. A potential explanation involved a canalization of the left-right asymmetry as a by-product of the parasite infection. Trematode infections were associated with different responses in valve width. Females infected by P. folium displayed significantly higher symmetry in valve width compared with non-infected congeners, whereas the infection involved an opposite pattern in males. B. polymorphus was also linked to a decrease in valve width asymmetry. This study suggested that a relationship exists between parasitism and shell morphology through the physiological condition of host zebra mussels. 相似文献
36.
37.
Kniazeff J Bessis AS Maurel D Ansanay H Prézeau L Pin JP 《Nature structural & molecular biology》2004,11(8):706-713
Membrane receptors, key components in signal transduction, often function as dimers. These include some G protein-coupled receptors such as metabotropic glutamate (mGlu) receptors that have large extracellular domains (ECDs) where agonists bind. How agonist binding in dimeric ECDs activates the effector domains remains largely unknown. The structure of the dimeric ECDs of mGlu(1) solved in the presence of agonist revealed two specific conformations in which either one or both protomers are in an agonist-stabilized closed form. Here we examined whether both conformations correspond to an active form of the full-length receptor. Using a system that allows the formation of dimers made of a wild-type and a mutant subunit, we show that the closure of one ECD per dimer is sufficient to activate the receptor, but the closure of both ECDs is required for full activity. 相似文献
38.
Goldstein DJ Fondrat C Muri F Nuel G Saragueta P Tocquet AS Prum B 《Comptes rendus biologies》2003,326(3):339-348
Inversions of short genomic sequences play a central role in the generation of protein complexity. More than half of the 1300 motifs registered in ProSite have protein inverse complementary sequences (princoms) among proteins registered in SwissProt. The observed number of princoms occurrences exceeds by far the expected number (p < 10(-10)). Princoms often endow their host proteins with a whole new range of biochemical and physiological capabilities, including the possibility of intramolecular and intermolecular disulfide bond formation. These results support the idea that, like the duplications, the inversions of small genomic fragments have been a fundamental mechanism for shaping genomes. 相似文献
39.
Petit H Nègre-Sadargues G Castillo R Valin S Trilles JP 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》1998,119(2):523-527
Penaeus japonicus postlarvae, reared under laboratory conditions, were fed an astaxanthin enriched diet to the investigate carotenoid metabolic capabilities during the postlarval development. Animals fed astaxanthin were found to absorb this carotenoid. The decrease of pigment concentration in the carotenoid starved group is related to the duration of the experimental feeding conditions; the carotenoid depletion depends upon the postlarval status at the starting point. As has been shown for adult prawns, the carotenoid pattern of postlarval stages, regardless of the diet, consists mainly of free and esterified astaxanthin; the relative amounts of these fractions undergo slight variations depending on the diet. 相似文献
40.
Anne-Sophie Borowiec Frédéric HagueValérie Gouilleux-Gruart Kaiss LassouedHalima Ouadid-Ahidouch 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(5):723-730
Insulin-like Growth Factor-1 (IGF-1) plays a key role in breast cancer development and cell cycle regulation. It has been demonstrated that IGF-1 stimulates cyclin expression, thus regulating the G1 to S phase transition of the cell cycle. Potassium (K+) channels are involved in the G1 phase progression of the cell cycle induced by growth factors. However, mechanisms that allow growth factors to cooperate with K+ channels in order to modulate the G1 phase progression and cyclin expression remain unknown. Here, we focused on hEag1 K+ channels which are over-expressed in breast cancer and are involved in the G1 phase progression of breast cancer cells (MCF-7). As expected, IGF-1 increased cyclin D1 and E expression of MCF-7 cells in a cyclic manner, whereas the increase of CDK4 and 2 levels was sustained. IGF-1 stimulated p21WAF1/Cip1 expression with a kinetic similar to that of cyclin D1, however p27Kip1 expression was insensitive to IGF-1. Interestingly, astemizole, a blocker of hEag1 channels, but not E4031, a blocker of HERG channels, inhibited the expression of both cyclins after 6-8 h of co-stimulation with IGF-1. However, astemizole failed to modulate CDK4, CDK2, p21WAF1/Cip1 and p27Kip1 expression. The down-regulation of hEag1 by siRNA provoked a decrease in cyclin expression. This study is the first to demonstrate that K+ channels such as hEag1 are directly involved in the IGF-1-induced up-regulation of cyclin D1 and E expression in MCF-7 cells. By identifying more specifically the temporal position of the arrest site induced by the inhibition of hEag1 channels, we confirmed that hEag1 activity is predominantly upstream of the arrest site induced by serum-deprivation, prior to the up-regulation of both cyclins D1 and E. 相似文献