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61.
Eun-Jung Kim Francisco J. Monje Lin Li Harald Höger Daniela D. Pollak Gert Lubec 《Cellular and molecular life sciences : CMLS》2013,70(4):743-759
The lymphocyte-specific protein tyrosine kinase (Lck), which belongs to the Src kinase-family, is expressed in neurons of the hippocampus, a structure critical for learning and memory. Recent evidence demonstrated a significant downregulation of Lck in Alzheimer’s disease. Lck has additionally been proposed to be a risk factor for Alzheimer’s disease, thus suggesting the involvement of Lck in memory function. The neuronal role of Lck, however, and its involvement in learning and memory remain largely unexplored. Here, in vitro electrophysiology, confocal microscopy, and molecular, pharmacological, genetic and biochemical techniques were combined with in vivo behavioral approaches to examine the role of Lck in the mouse hippocampus. Specific pharmacological inhibition and genetic silencing indicated the involvement of Lck in the regulation of neuritic outgrowth. In the functional pre-established synaptic networks that were examined electrophysiologically, specific Lck-inhibition also selectively impaired the long-term hippocampal synaptic plasticity without affecting spontaneous excitatory synaptic transmission or short-term synaptic potentiation. The selective inhibition of Lck also significantly altered hippocampus-dependent spatial learning and memory in vivo. These data provide the basis for the functional characterization of brain Lck, describing the importance of Lck as a critical regulator of both neuronal morphology and in vivo long-term memory. 相似文献
62.
Daniela Barretto Barbosa Trivella José Ribamar Ferreira-Júnior Laure Dumoutier Jean-Christophe Renauld Igor Polikarpov 《Cellular and molecular life sciences : CMLS》2010,67(17):2909-2935
The IL-10 family of cytokines is comprised of IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and IFN-λs (IL-28A, IL-28B, and IL-29).
The IL-10 family members bind to shared class II cytokine receptor chains that associate in various combinations in heterodimeric
complexes. Upon interleukin/receptor complex formation, these proteins switch on the Jak/STAT pathway and elicit pleiotropic
biological responses whose variety sharply contrasts with their structural similarities. IL-10 family members are involved
in several human diseases and health conditions and hence their structural analyses may provide valuable information to design
specific therapeutic strategies. In this review, we describe the human interleukin-10 family of cytokines, focusing on their
structures and functions, with particular attention given to IL-22 and IL-10. We report on the recently published structures
of IL-10 cytokine family members and their complexes with cognate transmembrane and soluble receptors as well as on interleukin
physiology and physiopathology. 相似文献
63.
Alessandra Tosco Maria Chiara Monti Bianca Fontanella Sandro Montefusco Luca D’Andrea Barbara Ziaco Daniela Baldantoni Marie-Christine Rio Liberato Marzullo 《Cellular and molecular life sciences : CMLS》2010,67(11):1943-1955
Trefoil protein 1 (TFF1) is a small secreted protein belonging to the trefoil factor family of proteins, that are present
mainly in the gastrointestinal (GI) tract and play pivotal roles as motogenic factors in epithelial restitution, cell motility,
and other incompletely characterized biological processes. We previously reported the up-regulation of TFF1 gene in copper
deficient rats and the unexpected property of the peptide to selectively bind copper. Following the previous evidence, here
we report the characterization of the copper binding site by fluorescence quenching spectroscopy and mass spectrometric analyses.
We demonstrate that Cys58 and at least three Glu surrounding residues surrounding it, are essential to efficiently bind copper.
Moreover, copper binding promotes the TFF1 homodimerization, thus increasing its motogenic activity in in vitro wound healing
assays. Copper levels could then modulate the TFF1 functions in the GI tract, as well as its postulated role in cancer progression
and invasion. 相似文献
64.
65.
Xu P Widmer G Wang Y Ozaki LS Alves JM Serrano MG Puiu D Manque P Akiyoshi D Mackey AJ Pearson WR Dear PH Bankier AT Peterson DL Abrahamsen MS Kapur V Tzipori S Buck GA 《Nature》2004,431(7012):1107-1112
Cryptosporidium species cause acute gastroenteritis and diarrhoea worldwide. They are members of the Apicomplexa--protozoan pathogens that invade host cells by using a specialized apical complex and are usually transmitted by an invertebrate vector or intermediate host. In contrast to other Apicomplexans, Cryptosporidium is transmitted by ingestion of oocysts and completes its life cycle in a single host. No therapy is available, and control focuses on eliminating oocysts in water supplies. Two species, C. hominis and C. parvum, which differ in host range, genotype and pathogenicity, are most relevant to humans. C. hominis is restricted to humans, whereas C. parvum also infects other mammals. Here we describe the eight-chromosome approximately 9.2-million-base genome of C. hominis. The complement of C. hominis protein-coding genes shows a striking concordance with the requirements imposed by the environmental niches the parasite inhabits. Energy metabolism is largely from glycolysis. Both aerobic and anaerobic metabolisms are available, the former requiring an alternative electron transport system in a simplified mitochondrion. Biosynthesis capabilities are limited, explaining an extensive array of transporters. Evidence of an apicoplast is absent, but genes associated with apical complex organelles are present. C. hominis and C. parvum exhibit very similar gene complements, and phenotypic differences between these parasites must be due to subtle sequence divergence. 相似文献
66.
V. Locatelli Daniela Cocchi S. Bajusz S. Spampinato E. E. Müller 《Cellular and molecular life sciences : CMLS》1978,34(12):1650-1651
Summary The growth hormone (GH) and prolactin releasing (PRL) activity of [D-Met2, Pro5]-enkephalinamide (EKNH2), an opioid peptide analog with higher opiate agonist activity that morphine, was compared in the unanesthetized male rat to those of equimolar doses of morphine upon systemic injection. EKNH2 proved to be a higher PRL, but not GH, releaser than the opiate alkaloid. 相似文献
67.
68.
Daniela Aparecida Savariz Bôlla Fernando Carvalho Jairo José Zocche Alexandre Bianco João Antônio de Bittencourt Vitto Raphael dos Santos 《Journal of Natural History》2017,51(47-48):2947-2953
Bats (Chiroptera), one of the most diverse groups in terms of taxonomy, morphology and ecology, are known for their nocturnal behaviour of flight and feeding. Although there is no consensus on the evolution of nocturnality in bats, many authors mention risk of predation, overheating, competition and mobbing by non-competitor species as arguments to justify nocturnal instead of daytime flight in bats. Herein we describe the first records of three genera of phyllostomid bats flying, foraging and drinking water during daytime in the Brazilian Amazon. All taxa were recorded drinking water, and some Phyllostomus sp. individuals were recorded foraging on termites, alongside birds. Risk of dehydration and overheating in roosts, as well as low competition in daytime, may explain the emergence of phyllostomid bats before sunset. 相似文献
69.
Yeager M Orr N Hayes RB Jacobs KB Kraft P Wacholder S Minichiello MJ Fearnhead P Yu K Chatterjee N Wang Z Welch R Staats BJ Calle EE Feigelson HS Thun MJ Rodriguez C Albanes D Virtamo J Weinstein S Schumacher FR Giovannucci E Willett WC Cancel-Tassin G Cussenot O Valeri A Andriole GL Gelmann EP Tucker M Gerhard DS Fraumeni JF Hoover R Hunter DJ Chanock SJ Thomas G 《Nature genetics》2007,39(5):645-649
Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 x 10(-13); heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13-1.41; homozygote OR: 1.58, 95% c.i.: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 x 10(-11); rs6983267 P = 6.62 x 10(-10)). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%). 相似文献
70.
A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer 总被引:28,自引:0,他引:28
Hunter DJ Kraft P Jacobs KB Cox DG Yeager M Hankinson SE Wacholder S Wang Z Welch R Hutchinson A Wang J Yu K Chatterjee N Orr N Willett WC Colditz GA Ziegler RG Berg CD Buys SS McCarty CA Feigelson HS Calle EE Thun MJ Hayes RB Tucker M Gerhard DS Fraumeni JF Hoover RN Thomas G Chanock SJ 《Nature genetics》2007,39(7):870-874
We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (P(trend) for the most strongly associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci. 相似文献