全文获取类型
收费全文 | 137篇 |
免费 | 0篇 |
专业分类
系统科学 | 5篇 |
教育与普及 | 1篇 |
理论与方法论 | 2篇 |
现状及发展 | 42篇 |
研究方法 | 26篇 |
综合类 | 58篇 |
自然研究 | 3篇 |
出版年
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2014年 | 5篇 |
2013年 | 3篇 |
2012年 | 14篇 |
2011年 | 13篇 |
2010年 | 9篇 |
2009年 | 1篇 |
2008年 | 11篇 |
2007年 | 6篇 |
2006年 | 9篇 |
2005年 | 7篇 |
2004年 | 8篇 |
2003年 | 6篇 |
2002年 | 5篇 |
2000年 | 1篇 |
1996年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1971年 | 4篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1966年 | 1篇 |
1960年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有137条查询结果,搜索用时 15 毫秒
121.
Kumar KA Sano G Boscardin S Nussenzweig RS Nussenzweig MC Zavala F Nussenzweig V 《Nature》2006,444(7121):937-940
Malaria infection starts when mosquitoes inject sporozoites into the skin. The parasites enter the blood stream and make their way to the liver where they develop into the exo-erythrocytic forms (EEFs). Immunization with irradiated sporozoites (IrSp) leads to robust protection against malaria infection in rodents, monkeys and humans by eliciting antibodies to circumsporozoite protein (CS) that inhibit sporozoite infectivity, and T cells that destroy the EEFs. To study the role of non-CS antigens in protection, we produced CS transgenic mice that were tolerant to CS T-cell epitopes. Here we show that in the absence of T-cell-dependent immune responses to CS, protection induced by immunization with two doses of IrSp was greatly reduced. Thus, although hundreds of other Plasmodium genes are expressed in sporozoites and EEFs, CS is a dominant protective antigen. Nevertheless, sterile immunity could be obtained by immunization of CS transgenics with three doses of IrSp. 相似文献
122.
Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. 总被引:28,自引:0,他引:28
Sergey Kalachikov Oleg Evgrafov Barbara Ross Melodie Winawer Christie Barker-Cummings Filippo Martinelli Boneschi Chang Choi Pavel Morozov Kamna Das Elita Teplitskaya Andrew Yu Eftihia Cayanis Graciela Penchaszadeh Andreas H Kottmann Timothy A Pedley W Allen Hauser Ruth Ottman T Conrad Gilliam 《Nature genetics》2002,30(3):335-341
The epilepsies are a common, clinically heterogeneous group of disorders defined by recurrent unprovoked seizures. Here we describe identification of the causative gene in autosomal-dominant partial epilepsy with auditory features (ADPEAF, MIM 600512), a rare form of idiopathic lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. We constructed a complete, 4.2-Mb physical map across the genetically implicated disease-gene region, identified 28 putative genes (Fig. 1) and resequenced all or part of 21 genes before identifying presumptive mutations in one copy of the leucine-rich, glioma-inactivated 1 gene (LGI1) in each of five families with ADPEAF. Previous studies have indicated that loss of both copies of LGI1 promotes glial tumor progression. We show that the expression pattern of mouse Lgi1 is predominantly neuronal and is consistent with the anatomic regions involved in temporal lobe epilepsy. Discovery of LGI1 as a cause of ADPEAF suggests new avenues for research on pathogenic mechanisms of idiopathic epilepsies. 相似文献
123.
Types of cell contacts in arterial smooth muscle 总被引:1,自引:0,他引:1
Ruth M. Henderson 《Cellular and molecular life sciences : CMLS》1975,31(1):103-105
Zusammenfassung Nachweis, dass in Arteriolen sowie in präkapillaren Arteriolen des Hunde-Duodenums nur eine einfache Aneinanderlagerung der Muskelzellen erfolgt und keine gap junctions, wie sie in den Muskelschichten der Hohlwandorgane vorhanden sind. 相似文献
124.
Normalization of current kinetics by interaction between the alpha 1 and beta subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel. 总被引:14,自引:0,他引:14
A E Lacerda H S Kim P Ruth E Perez-Reyes V Flockerzi F Hofmann L Birnbaumer A M Brown 《Nature》1991,352(6335):527-530
Purification of skeletal muscle dihydropyridine binding sites has enabled protein complexes to be isolated from which Ca2+ currents have been reconstituted. Complementary DNAs encoding the five subunits of the dihydropyridine receptor, alpha 1, beta, gamma, alpha 2 and delta, have been cloned and it is now recognized that alpha 2 and delta are derived from a common precursor. The alpha 1 subunit can itself produce Ca2+ currents, as was demonstrated using mouse L cells lacking alpha 2 delta, beta and gamma (our unpublished results). In L cells, stable expression of skeletal muscle alpha 1 alone was sufficient to generate voltage-sensitive, high-threshold L-type Ca2+ channel currents which were dihydropyridine-sensitive and blocked by Cd2+, but the activation kinetics were about 100 times slower than expected for skeletal muscle Ca2+ channel currents. This could have been due to the cell type in which alpha 1 was being expressed or to the lack of a regulatory component particularly one of the subunits that copurifies with alpha 1. We show here that coexpression of skeletal muscle beta with skeletal muscle alpha 1 generates cell lines expressing Ca2+ channel currents with normal activation kinetics as evidence for the participation of the dihydropyridine-receptor beta subunits in the generation of skeletal muscle Ca2+ channel currents. 相似文献
125.
The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity. 相似文献
126.
127.
Zenker M Mayerle J Lerch MM Tagariello A Zerres K Durie PR Beier M Hülskamp G Guzman C Rehder H Beemer FA Hamel B Vanlieferinghen P Gershoni-Baruch R Vieira MW Dumic M Auslender R Gil-da-Silva-Lopes VL Steinlicht S Rauh M Shalev SA Thiel C Ekici AB Winterpacht A Kwon YT Varshavsky A Reis A 《Nature genetics》2005,37(12):1345-1350
Johanson-Blizzard syndrome (OMIM 243800) is an autosomal recessive disorder that includes congenital exocrine pancreatic insufficiency, multiple malformations such as nasal wing aplasia, and frequent mental retardation. We mapped the disease-associated locus to chromosome 15q14-21.1 and identified mutations, mostly truncating ones, in the gene UBR1 in 12 unrelated families with Johanson-Blizzard syndrome. UBR1 encodes one of at least four functionally overlapping E3 ubiquitin ligases of the N-end rule pathway, a conserved proteolytic system whose substrates include proteins with destabilizing N-terminal residues. Pancreas of individuals with Johanson-Blizzard syndrome did not express UBR1 and had intrauterine-onset destructive pancreatitis. In addition, we found that Ubr1(-/-) mice, whose previously reported phenotypes include reduced weight and behavioral abnormalities, had an exocrine pancreatic insufficiency, with impaired stimulus-secretion coupling and increased susceptibility to pancreatic injury. Our findings indicate that deficiency of UBR1 perturbs the pancreas' acinar cells and other organs, presumably owing to metabolic stabilization of specific substrates of the N-end rule pathway. 相似文献
128.
Outbred mouse stocks, often used in genetics, toxicology and pharmacology research, have been generated in rather haphazard ways. Understanding the characteristics of these stocks and their advantages and disadvantages is important for experimental design. In many studies these mice are used inappropriately, wasting animals' lives and resources on suboptimal experiments. Recently, however, researchers from the field of complex trait analysis have capitalized on the genetics of outbred stocks to refine the identification of quantitative trait loci. Here we assess the most widely used outbred stocks of mice and present guidelines for their use. 相似文献
129.
130.
Englund C Lorén CE Grabbe C Varshney GK Deleuil F Hallberg B Palmer RH 《Nature》2003,425(6957):512-516
The Drosophila melanogaster gene Anaplastic lymphoma kinase (Alk) is homologous to mammalian Alk, a member of the Alk/Ltk family of receptor tyrosine kinases (RTKs). We have previously shown that the Drosophila Alk RTK is crucial for visceral mesoderm development during early embryogenesis. Notably, observed Alk visceral mesoderm defects are highly reminiscent of the phenotype reported for the secreted molecule Jelly belly (Jeb). Here we show that Drosophila Alk is the receptor for Jeb in the developing visceral mesoderm, and that Jeb binding stimulates an Alk-driven, extracellular signal-regulated kinase-mediated signalling pathway, which results in the expression of the downstream gene duf (also known as kirre)--needed for muscle fusion. This new signal transduction pathway drives specification of the muscle founder cells, and the regulation of Duf expression by the Drosophila Alk RTK explains the visceral-mesoderm-specific muscle fusion defects observed in both Alk and jeb mutant animals. 相似文献