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91.
Inhibitory effect of actinomycin D on tail atrophy in Xenopus larvae at metamorphosis 总被引:2,自引:0,他引:2
R Weber 《Experientia》1965,21(11):665-666
92.
Kaminsky R Ducray P Jung M Clover R Rufener L Bouvier J Weber SS Wenger A Wieland-Berghausen S Goebel T Gauvry N Pautrat F Skripsky T Froelich O Komoin-Oka C Westlund B Sluder A Mäser P 《Nature》2008,452(7184):176-180
Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics--the benzimidazoles, imidazothiazoles and macrocyclic lactones--has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics. 相似文献
93.
Wingert RA Galloway JL Barut B Foott H Fraenkel P Axe JL Weber GJ Dooley K Davidson AJ Schmid B Schmidt B Paw BH Shaw GC Kingsley P Palis J Schubert H Chen O Kaplan J Zon LI;Tübingen Screen Consortium 《Nature》2005,436(7053):1035-1039
Iron is required to produce haem and iron-sulphur (Fe-S) clusters, processes thought to occur independently. Here we show that the hypochromic anaemia in shiraz (sir) zebrafish mutants is caused by deficiency of glutaredoxin 5 (grx5), a gene required in yeast for Fe-S cluster assembly. We found that grx5 was expressed in erythroid cells of zebrafish and mice. Zebrafish grx5 rescued the assembly of grx5 yeast Fe-S, showing that the biochemical function of grx5 is evolutionarily conserved. In contrast to yeast, vertebrates use iron regulatory protein 1 (IRP1) to sense intracellular iron and regulate mRNA stability or the translation of iron metabolism genes. We found that loss of Fe-S cluster assembly in sir animals activated IRP1 and blocked haem biosynthesis catalysed by aminolaevulinate synthase 2 (ALAS2). Overexpression of ALAS2 RNA without the 5' iron response element that binds IRP1 rescued sir embryos, whereas overexpression of ALAS2 including the iron response element did not. Further, antisense knockdown of IRP1 restored sir embryo haemoglobin synthesis. These findings uncover a connection between haem biosynthesis and Fe-S clusters, indicating that haemoglobin production in the differentiating red cell is regulated through Fe-S cluster assembly. 相似文献
94.
An electron propagating through a solid carries spin angular momentum in addition to its mass and charge. Of late there has been considerable interest in developing electronic devices based on the transport of spin that offer potential advantages in dissipation, size and speed over charge-based devices. However, these advantages bring with them additional complexity. Because each electron carries a single, fixed value (- e) of charge, the electrical current carried by a gas of electrons is simply proportional to its total momentum. A fundamental consequence is that the charge current is not affected by interactions that conserve total momentum, notably collisions among the electrons themselves. In contrast, the electron's spin along a given spatial direction can take on two values, +/- [planck]/2 (conventionally upward arrow, downward arrow), so that the spin current and momentum need not be proportional. Although the transport of spin polarization is not protected by momentum conservation, it has been widely assumed that, like the charge current, spin current is unaffected by electron-electron (e-e) interactions. Here we demonstrate experimentally not only that this assumption is invalid, but also that over a broad range of temperature and electron density, the flow of spin polarization in a two-dimensional gas of electrons is controlled by the rate of e-e collisions. 相似文献
95.
Fractionated X-irradiation of mouse fetuses on gestation days 11-13 resulted in a significantly increased postnatal mortality of female litters. This occurred only at 3 x 110 rad, which was the threshold for the formation of typical neuroepithelial, rosette-like malformations. 相似文献
96.
Greenland Eskimos who live on a traditional marine diet rich in long chain omega 3-polyunsaturated fatty acids have a low incidence of cardiovascular disease and myocardial infarction. In their plasma and platelet lipids, arachidonic acid, the precursor of dienoic prostanoids, is partly replaced by eicosapentaenoic acid (C20:5, omega 3; EPA), the precursor of trienoic prostanoids. Studies with an Eskimo diet or a Western diet supplemented with sea fish or fish oil rich in EPA resulted in an 'Eskimo-like' pattern of plasma and platelet lipids. Moreover, less reactive platelets, a reduced ex vivo formation of proaggregatory thromboxane A2 and a blunted circulatory response to pressor hormones were reported. These favourable functional effects may be induced by a shift of prostanoid formation from the dienoic to the trienoic series. We show here that the major urinary metabolite of endogenous prostaglandin I3 is present in subjects that have ingested either cod liver oil (approximately 4 g EPA per day) or mackerel (approximately 10-15 g EPA per day). Our studies provide the first direct evidence for in vivo formation of prostaglandin I3 in man. 相似文献
97.
Johannessen CM Boehm JS Kim SY Thomas SR Wardwell L Johnson LA Emery CM Stransky N Cogdill AP Barretina J Caponigro G Hieronymus H Murray RR Salehi-Ashtiani K Hill DE Vidal M Zhao JJ Yang X Alkan O Kim S Harris JL Wilson CJ Myer VE Finan PM Root DE Roberts TM Golub T Flaherty KT Dummer R Weber BL Sellers WR Schlegel R Wargo JA Hahn WC Garraway LA 《Nature》2010,468(7326):968-972
Oncogenic mutations in the serine/threonine kinase B-RAF (also known as BRAF) are found in 50-70% of malignant melanomas. Pre-clinical studies have demonstrated that the B-RAF(V600E) mutation predicts a dependency on the mitogen-activated protein kinase (MAPK) signalling cascade in melanoma-an observation that has been validated by the success of RAF and MEK inhibitors in clinical trials. However, clinical responses to targeted anticancer therapeutics are frequently confounded by de novo or acquired resistance. Identification of resistance mechanisms in a manner that elucidates alternative 'druggable' targets may inform effective long-term treatment strategies. Here we expressed ~600 kinase and kinase-related open reading frames (ORFs) in parallel to interrogate resistance to a selective RAF kinase inhibitor. We identified MAP3K8 (the gene encoding COT/Tpl2) as a MAPK pathway agonist that drives resistance to RAF inhibition in B-RAF(V600E) cell lines. COT activates ERK primarily through MEK-dependent mechanisms that do not require RAF signalling. Moreover, COT expression is associated with de novo resistance in B-RAF(V600E) cultured cell lines and acquired resistance in melanoma cells and tissue obtained from relapsing patients following treatment with MEK or RAF inhibitors. We further identify combinatorial MAPK pathway inhibition or targeting of COT kinase activity as possible therapeutic strategies for reducing MAPK pathway activation in this setting. Together, these results provide new insights into resistance mechanisms involving the MAPK pathway and articulate an integrative approach through which high-throughput functional screens may inform the development of novel therapeutic strategies. 相似文献
98.
Wildland shrubs have gained considerable attention in recent years due to increasing recognition of their values as animal feed, as wildlife habitat, and for land reclamation. Better management of the shrub resource will be possible through clearer taxonomic identification and better understanding of phylogenetic relationships. This study applied polyacrylamide gel electrophoresis and further developed this technique to address genetic relationships among 16 paired shrub species (genera: Artemisia, Chrysothamnus, Atriplex, Ceratoides, Sarcobatus, Purshia, Cowania, and Cercocarpus [Compositae, Chenopodiaceae, Rosaceae]). Cluster analysis of similarity values for total protein and 14 isoenzyme systems gave patterns of species relationships expected from classical morphological grounds with two minor exceptions. Isoenzyme analyses showed promise for solving taxonomic, phylogenetic, and population genetics problems. 相似文献
99.
Physiological responses of Allenrolfea occidentalis to salinity and seedling density were investigated. Effects of salinity (0, 200, 400, 600, 800, and 1000 mM NaCl) and 3 planting densities (2000, 4000, 6000 plants m -2 ) on the growth, survival, and ecophysiology of A. occidentalis , a stem succulent inland halophyte, were studied under controlled greenhouse conditions. Plants were grown in a sand culture using subirrigation. Dry mass of roots was highest at 600 mM NaCl at low density (2000 plants m -2 ), but declined as salinity increased. Tissue water content was highest at the 200 mM NaCl treatment and decreased with increased salinity. Water potential of the plants became more negative with increasing salinity due to the accumulation of NaCl in the leaves. Inorganic ions, especially Na + and Cl - , contributed substantially to dry mass. Na + and Cl - concentration in shoots and roots increased when NaCl level was increased while K + , Ca ++ , Mg ++ , SO 4 -- , and NO 3 - contents decreased. Net photosynthesis increased at low salinity (200 mM), but photosynthesis at other salinities was not significantly different from the control. While A. occidentalis is very salt tolerant and photosynthesis functioned reasonably well at high salinities, extremely high salinity did decrease dry mass of roots and shoots. 相似文献
100.