全文获取类型
收费全文 | 969篇 |
免费 | 93篇 |
国内免费 | 1篇 |
出版年
2022年 | 8篇 |
2021年 | 22篇 |
2020年 | 8篇 |
2019年 | 16篇 |
2018年 | 14篇 |
2017年 | 8篇 |
2016年 | 32篇 |
2015年 | 40篇 |
2014年 | 43篇 |
2013年 | 59篇 |
2012年 | 69篇 |
2011年 | 48篇 |
2010年 | 41篇 |
2009年 | 40篇 |
2008年 | 54篇 |
2007年 | 58篇 |
2006年 | 46篇 |
2005年 | 52篇 |
2004年 | 52篇 |
2003年 | 51篇 |
2002年 | 39篇 |
2001年 | 17篇 |
2000年 | 6篇 |
1999年 | 9篇 |
1998年 | 8篇 |
1997年 | 15篇 |
1996年 | 11篇 |
1994年 | 10篇 |
1993年 | 9篇 |
1992年 | 6篇 |
1991年 | 10篇 |
1990年 | 7篇 |
1989年 | 6篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 10篇 |
1984年 | 8篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1981年 | 8篇 |
1980年 | 7篇 |
1977年 | 5篇 |
1975年 | 4篇 |
1974年 | 9篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1971年 | 6篇 |
1970年 | 5篇 |
1969年 | 7篇 |
1968年 | 4篇 |
排序方式: 共有1063条查询结果,搜索用时 93 毫秒
101.
Anna?Lucea Carlos M.?DuarteEmail author Susana?Agustí Hilary?Kennedy 《Biogeochemistry》2005,73(2):303-323
The dynamics of the nutrient pools and their stoichiometry as well as their control by ecosystem metabolism (benthic and planktonic)
and benthic–pelagic exchanges (sedimentation rates and sediment waterfluxes) were examined in the Mediterranean littoral (Blanes
Bay, NE Spain). Dissolved organic nitrogen comprised about half of the nitrogen present in the water column and the carbon
pool was dominated by the inorganic pool (95% of the carbon present in the water column). The dissolved and particulate organic
pools were deficient in P relative to C and N, indicating a rapid recycling of P from organic matter. The pelagic compartment
was heterotrophic, supported by significant allochthonous inputs of land material, which also contributed greatly to the sedimentary
inputs (37% of total sedimenting carbon). In contrast, the benthic compartment was autotrophic, with the excess net benthic
community production balancing the deficit in pelagic community production, leading to metabolic equilibrium at the station
studied. Sedimentary inputs of nitrogen, phosphorus and silicon exceeded the benthic release, indicating that the benthic
compartment acted as a sink for nutrients, consistent with its autotrophic nature. Carbon inputs to the benthic compartment
also exceeded requirements, due to the allochthonous subsidies to the system, so that the benthic compartment stored or exported
organic carbon.
An erratum to this article can be found at . 相似文献
102.
103.
Background
A single base pair mutation in the sodium channel confers knock-down resistance to pyrethroids in many insect species. Its occurrence in Anopheles mosquitoes may have important implications for malaria vector control especially considering the current trend for large scale pyrethroid-treated bednet programmes. Screening Anopheles gambiae populations for the kdr mutation has become one of the mainstays of programmes that monitor the development of insecticide resistance. The screening is commonly performed using a multiplex Polymerase Chain Reaction (PCR) which, since it is reliant on a single nucleotide polymorphism, can be unreliable. Here we present a reliable and potentially high throughput method for screening An. gambiae for the kdr mutation.Methods
A Hot Ligation Oligonucleotide Assay (HOLA) was developed to detect both the East and West African kdr alleles in the homozygous and heterozygous states, and was optimized for use in low-tech developing world laboratories. Results from the HOLA were compared to results from the multiplex PCR for field and laboratory mosquito specimens to provide verification of the robustness and sensitivity of the technique.Results and Discussion
The HOLA assay, developed for detection of the kdr mutation, gives a bright blue colouration for a positive result whilst negative reactions remain colourless. The results are apparent within a few minutes of adding the final substrate and can be scored by eye. Heterozygotes are scored when a sample gives a positive reaction to the susceptible probe and the kdr probe. The technique uses only basic laboratory equipment and skills and can be carried out by anyone familiar with the Enzyme-linked immunosorbent assay (ELISA) technique. A comparison to the multiplex PCR method showed that the HOLA assay was more reliable, and scoring of the plates was less ambiguous.Conclusion
The method is capable of detecting both the East and West African kdr alleles in the homozygous and heterozygous states from fresh or dried material using several DNA extraction methods. It is more reliable than the traditional PCR method and may be more sensitive for the detection of heterozygotes. It is inexpensive, simple and relatively safe making it suitable for use in resource-poor countries. 相似文献104.
105.
A bacterial glutathione transporter (Escherichia coli CydDC) exports reductant to the periplasm 总被引:1,自引:0,他引:1
Glutathione (GSH), a major biological antioxidant, maintains redox balance in prokaryotes and eukaryotic cells and forms exportable conjugates with compounds of pharmacological and agronomic importance. However, no GSH transporter has been characterized in a prokaryote. We show here that a heterodimeric ATP-binding cassette-type transporter, CydDC, mediates GSH transport across the Escherichia coli cytoplasmic membrane. In everted membrane vesicles, GSH is imported via an ATP-driven, protonophore-insensitive, orthovanadate-sensitive mechanism, equating with export to the periplasm in intact cells. GSH transport and cytochrome bd quinol oxidase assembly are abolished in the cydD1 mutant. Glutathione disulfide (GSSG) was not transported in either Cyd(+) or Cyd(-) strains. Exogenous GSH restores defective swarming motility and benzylpenicillin sensitivity in a cydD mutant and also benzylpenicillin sensitivity in a gshA mutant defective in GSH synthesis. Overexpression of the cydDC operon in dsbD mutants defective in disulfide bond formation restores dithiothreitol tolerance and periplasmic cytochrome b assembly, revealing redundant pathways for reductant export to the periplasm. These results identify the first prokaryotic GSH transporter and indicate a key role for GSH in periplasmic redox homeostasis. 相似文献
106.
107.
Wondji CS Hunt RH Pignatelli P Steen K Coetzee M Besansky N Lobo N Collins FH Hemingway J Ranson H 《Genetics》2005,171(4):1779-1787
We have constructed a genetic map of the major African malaria vector, Anopheles funestus, using genetic markers segregating in F(2) progeny from crosses between two strains colonized from different field sites. Genotyping was performed on 174 progeny from three families using 33 microsatellite markers, a single RFLP, and 15 single nucleotide polymorphism (SNP) loci. Four linkage groups were resolved and these were anchored to chromosomes X and 2 and chromosomal arms 3R and 3L by comparison with a physical map of this species. Five markers were linked to the X chromosome, 16 markers to chromosome 2, and 10 and 11 markers to chromosomal arms 3R and 3L, respectively. This significantly increases the number of chromosomally defined genetic markers for this species and will facilitate the identification of genes controlling epidemiologically important traits such as resistance to insecticides or vector competence. 相似文献
108.
Coon H Matsunami N Stevens J Miller J Pingree C Camp NJ Thomas A Krasny L Lainhart J Leppert MF McMahon W 《Human heredity》2005,60(4):220-226
Though autism shows strong evidence for genetic etiology, specific genes have not yet been found. We tested for linkage in a candidate region on chromosome 3q25-27 first identified in Finnish autism families [1]. The peak in this previous study was at D3S3037 (183.9 cM). We tested this region in seven affected family members and 24 of their relatives from a single large extended Utah pedigree of Northern European ancestry. A total of 70 single nucleotide polymorphisms (SNPs) were analyzed from 165 to 204 cM. The maximum NPL-all nonparametric score using SimWalk2snp was 3.53 (empirical p val ue = 0.0003) at 185.2 cM (SNP rs1402229), close to the Finnish peak. A secondary analysis using MCLINK supported this result, with a maximum of 3.92 at 184.6 cM (SNP rs1362645). We tested for alterations in a candidate gene in this region, the fragile X autosomal homolog, FXR1. No variants likely to contribute to autism were found in the coding sequence, exon-intron boundaries, or the promoter region of this gene. 相似文献
109.
In budding yeast, Cla4 and Ste20, two p21-activated kinases, contribute to numerous morphogenetic processes. Loss of Ste20 or Cla4 individually confers distinct phenotypes, implying that they regulate different processes. However, loss of both proteins is lethal, suggesting some functional overlap. To explore the role(s) of Cla4, we and others have sought mutations that are lethal in a cla4 Delta strain. These mutations define >60 genes. Recently, both Ste20 and Cla4 have been implicated in mitotic exit. Here, we identify a genetic interaction between PHO85, which encodes a cyclin-dependent kinase, and CLA4. We further show that the Pho85-coupled G(1) cyclins Pcl1 and Pcl2 contribute to this Pho85 role. We performed a two-hybrid screen with Pcl1. Three Pcl1-interacting proteins were identified: Ncp1, Hms1, and a novel ATPase dubbed Epa1. Each of these proteins interacts with Pcl1 in GST pull-down experiments and is specifically phosphorylated by Pcl1.Pho85 complexes. NCP1, HMS1, and EPA1 also genetically interact with CLA4. Like Cla4, the proteins Hms1, Ncp1, and Pho85 appear to affect mitotic exit, a conclusion that follows from the mislocalization of Cdc14, a key mitotic regulator, in strains lacking these proteins. We propose a model in which the G(1) Pcl1.Pho85 complex regulates mitotic exit machinery. 相似文献
110.
Böhm E Sturm GJ Weiglhofer I Sandig H Shichijo M McNamee A Pease JE Kollroser M Peskar BA Heinemann A 《The Journal of biological chemistry》2004,279(9):7663-7670
Thromboxane (TX) A(2), a cyclooxygenase-derived mediator involved in allergic responses, is rapidly converted in vivo to a stable metabolite, 11-dehydro-TXB(2), which is considered to be biologically inactive. In this study, we found that 11-dehydro-TXB(2), but not the TXA(2) analogue U46,619 or TXB(2), activated eosinophils and basophils, as assayed by flow cytometric shape change. 11-Dehydro-TXB(2) was also chemotactic for eosinophils but did not induce, nor inhibit, platelet aggregation. Chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) is an important chemoattractant receptor expressed by eosinophils, basophils, and TH2 lymphocytes, and prostaglandin (PG)D(2) has been shown to be its principal ligand. 11-Dehydro-TXB(2) induced calcium flux mainly from intracellular stores in eosinophils, and this response was desensitized after stimulation with PGD(2) but not other eosinophil chemoattractants. Shape change responses of eosinophils and basophils to 11-dehydro-TXB(2) were inhibited by the thromboxane (TP)/CRTH2 receptor antagonist ramatroban, but not the selective TP antagonist SQ29,548, and were insensitive to pertussis toxin. The phospholipase C inhibitor U73,122 attenuated both 11-dehydro-TXB(2)- and PGD(2)-induced shape change. 11-Dehydro-TXB(2) also induced the chemotaxis of BaF/3 cells transfected with hCRTH2 but not naive BaF/3 cells. At a threshold concentration, 11-dehydro-TXB(2) had no antagonistic effect on CRTH2-mediated responses as induced by PGD2. These data show that 11-dehydro-TXB(2) is a full agonist of the CRTH2 receptor and hence might cause CRTH2 activation in cellular contexts where PGD-synthase is not present. Given its production in the allergic lung, antagonism of the 11-dehydro-TXB(2)/CRTH2axis may be of therapeutic relevance. 相似文献