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61.
Brigitte Cambon de Lavalette Charles Tijus Christine Leproux Olivier Bauer 《Foundations of Science》2005,10(1):25-45
Taxonomy Based modeling was applied to describe drivers’ mental models of variable message signs (VMS’s) displayed on expressways.
Progress in road telematics has made it possible to introduce variable message signs (VMS’s). Sensors embedded in the carriageway
every 500m record certain variables (speed, flow rate, etc.) that are transformed in real time into “driving times” to a given
destination if road conditions do not change.
VMS systems are auto-regulative Man-Machine (AMMI) systems which incorporate a model of the user: if the traffic flow is too
high, then drivers should choose alternative routes. In so doing, the traffic flow should decrease. The model of the user
is based on suppositions such as: people do not like to waste time, they fully understand the displayed messages, they trust
the displayed values, they know of alternative routes. However, people also have a model of the way the system functions.
And if they do not believe the contents of the message, they will not act as expected.
We collected data through interviews with drivers using the critical incidents technique (Flanagan, 1985). Results show that
the mental models that drivers have of the way the VMS system works are various but not numerous and that most of them differ
from the“ideal expert” mental model. It is clear that users don’t have an adequate model of how the VMS system works and that
VMS planners have a model of user behaviour that does not correspond to the behaviour of the drivers we interviewed. Finally,
Taxonomy Based Modeling is discussed as a tool for mental model remediation. 相似文献
62.
Defects in whirlin,a PDZ domain molecule involved in stereocilia elongation,cause deafness in the whirler mouse and families with DFNB31 总被引:22,自引:0,他引:22
Mburu P Mustapha M Varela A Weil D El-Amraoui A Holme RH Rump A Hardisty RE Blanchard S Coimbra RS Perfettini I Parkinson N Mallon AM Glenister P Rogers MJ Paige AJ Moir L Clay J Rosenthal A Liu XZ Blanco G Steel KP Petit C Brown SD 《Nature genetics》2003,34(4):421-428
The whirler mouse mutant (wi) does not respond to sound stimuli, and detailed ultrastructural analysis of sensory hair cells in the organ of Corti of the inner ear indicates that the whirler gene encodes a protein involved in the elongation and maintenance of stereocilia in both inner hair cells (IHCs) and outer hair cells (OHCs). BAC-mediated transgene correction of the mouse phenotype and mutation analysis identified the causative gene as encoding a novel PDZ protein called whirlin. The gene encoding whirlin also underlies the human autosomal recessive deafness locus DFNB31. In the mouse cochlea, whirlin is expressed in the sensory IHC and OHC stereocilia. Our findings suggest that this novel PDZ domain-containing molecule acts as an organizer of submembranous molecular complexes that control the coordinated actin polymerization and membrane growth of stereocilia. 相似文献
63.
Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis 总被引:10,自引:0,他引:10
Parviz F Matullo C Garrison WD Savatski L Adamson JW Ning G Kaestner KH Rossi JM Zaret KS Duncan SA 《Nature genetics》2003,34(3):292-296
Although advances have been made in understanding cell differentiation, only rudimentary knowledge exists concerning how differentiated cells form tissues and organs. We studied liver organogenesis because the cell and tissue architecture of this organ is well defined. Approximately 60% of the adult liver consists of hepatocytes that are arranged as single-cell anastomosing plates extending from the portal region of the liver lobule toward the central vein. The basal surface of the hepatocytes is separated from adjacent sinusoidal endothelial cells by the space of Disse, where the exchange of substances between serum and hepatocytes takes place. The hepatocyte's apical surface forms bile canaliculi that transport bile to the hepatic ducts. Proper liver architecture is crucial for hepatic function and is commonly disrupted in disease states, including cirrhosis and hepatitis. Here we report that hepatocyte nuclear factor 4alpha (Hnf4alpha) is essential for morphological and functional differentiation of hepatocytes, accumulation of hepatic glycogen stores and generation of a hepatic epithelium. We show that Hnf4alpha is a dominant regulator of the epithelial phenotype because its ectopic expression in fibroblasts induces a mesenchymal-to-epithelial transition. Most importantly, the morphogenetic parameters controlled by Hnf4alpha in hepatocytes are essential for normal liver architecture, including the organization of the sinusoidal endothelium. 相似文献
64.
The production of defects in flow-aligning nematic liquid crystals under simple shear flow is analyzed by linear stability analysis based on Leslie-Ericksen theory. It is pointed out that the equation of motion of the nematic director under simple shear flow conforms to the driven over-damped sine-Gordon equation and has a soliton solution of amplitude π. It has also been shown that the stationary state with the director uniformly oriented at a Leslie angle is only a metastable state and that the potential, which governs the motion of the director, has infinite numbers of stable stationary states. Therefore, the defects, appearing as a stable solitary solution, can be nucleated from a uniformly aligned flow-aligning type of nematic liquid crystal by shear flow. On the other hand, the bands with long axis parallel to the vorticity axis, appearing as an unstable solution, can be observed as transient patterns at low shear rate and low shear strain value. The theoretical predictions are compared with previous experimental observations. 相似文献
65.
Kenia Pedrosa Nunes Christine S. Rigsby R. Clinton Webb 《Cellular and molecular life sciences : CMLS》2010,67(22):3823-3836
RhoA/Rho-kinase pathway plays an important role in many pathological conditions. RhoA participates in the regulation of smooth
muscle tone and activates many downstream kinases. The best characterized are the serine/threonine kinase isoforms (Rho-kinase
or ROCK), ROCKα/ROCK2 and ROCKβ/ROCK1. ROCK is necessary for diverse functions such as local blood flow, arterial/pulmonary
blood pressure, airway resistance and intestinal peristalsis. ROCK activation permits actin/myosin interactions and smooth
muscle cells contraction by maintaining the activity of myosin light-chain kinase, independently of the free cytosolic calcium
level. The sensitization of smooth muscle myofilaments to calcium has been implicated in many pathological states, such as
hypertension, diabetes, heart attack, stroke, pulmonary hypertension, erectile dysfunction, and cancer. The focus of this
review is on the involvement of RhoA/Rho-kinase in diseases. We will briefly describe the ROCK isoforms and the role of RhoA/Rho-kinase
in the vasculature, before exploring the most recent findings regarding this pathway and various diseases. 相似文献
66.
Carninci P Sandelin A Lenhard B Katayama S Shimokawa K Ponjavic J Semple CA Taylor MS Engström PG Frith MC Forrest AR Alkema WB Tan SL Plessy C Kodzius R Ravasi T Kasukawa T Fukuda S Kanamori-Katayama M Kitazume Y Kawaji H Kai C Nakamura M Konno H Nakano K Mottagui-Tabar S Arner P Chesi A Gustincich S Persichetti F Suzuki H Grimmond SM Wells CA Orlando V Wahlestedt C Liu ET Harbers M Kawai J Bajic VB Hume DA Hayashizaki Y 《Nature genetics》2006,38(6):626-635
67.
This study examined the role of Rab5a GTPase in regulating hCG-induced internalization and trafficking of the hCG-LH receptor
complex in transfected 293T cells. Coexpression of wild-type Rab5a (WT) or constitutively active Rab5a (Q79L) with LHR significantly
increased hCG-induced LHR internalization. Conversely, coexpression of dominant negative Rab5a (S34N) with LHR reduced internalization.
Confocal microscopy showed LHR colocalizing with Rab5a (WT) and Rab5a (Q79L) in punctuate structures. Coexpression of Rab5a
(WT) and Rab5a (Q79L) with LHR significantly increased colocalization of LHR in early endosomes. Conversely, dominant negative
Rab5a (S34N) decreased this colocalization. While Rab5a stimulated internalization of LHR, it significantly decreased LHR
recycling to the cell surface and increased degradation. Dominant negative Rab5a (S34N) increased LHR recycling and decreased
degradation. These results suggest that Rab5a plays a role in LHR trafficking by facilitating internalization and fusion to
early endosomes, increasing the degradation of internalized receptor resulting in a reduction in LHR recycling. 相似文献
68.
Rivas MA Beaudoin M Gardet A Stevens C Sharma Y Zhang CK Boucher G Ripke S Ellinghaus D Burtt N Fennell T Kirby A Latiano A Goyette P Green T Halfvarson J Haritunians T Korn JM Kuruvilla F Lagacé C Neale B Lo KS Schumm P Törkvist L;National Institute of Diabetes Digestive Kidney Diseases Inflammatory Bowel Disease Genetics Consortium 《Nature genetics》2011,43(11):1066-1073
More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 × 10(-16), odds ratio ≈ 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models. 相似文献
69.
TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis 总被引:2,自引:0,他引:2
Kabashi E Valdmanis PN Dion P Spiegelman D McConkey BJ Vande Velde C Bouchard JP Lacomblez L Pochigaeva K Salachas F Pradat PF Camu W Meininger V Dupre N Rouleau GA 《Nature genetics》2008,40(5):572-574
Recently, TDP-43 was identified as a key component of ubiquitinated aggregates in amyotrophic lateral sclerosis (ALS), an adult-onset neurological disorder that leads to the degeneration of motor neurons. Here we report eight missense mutations in nine individuals--six from individuals with sporadic ALS (SALS) and three from those with familial ALS (FALS)--and a concurring increase of a smaller TDP-43 product. These findings further corroborate that TDP-43 is involved in ALS pathogenesis. 相似文献
70.
Park CC Ahn S Bloom JS Lin A Wang RT Wu T Sekar A Khan AH Farr CJ Lusis AJ Leahy RM Lange K Smith DJ 《Nature genetics》2008,40(4):421-429
We mapped regulatory loci for nearly all protein-coding genes in mammals using comparative genomic hybridization and expression array measurements from a panel of mouse-hamster radiation hybrid cell lines. The large number of breaks in the mouse chromosomes and the dense genotyping of the panel allowed extremely sharp mapping of loci. As the regulatory loci result from extra gene dosage, we call them copy number expression quantitative trait loci, or ceQTLs. The -2log10P support interval for the ceQTLs was <150 kb, containing an average of <2-3 genes. We identified 29,769 trans ceQTLs with -log10P > 4, including 13 hotspots each regulating >100 genes in trans. Further, this work identifies 2,761 trans ceQTLs harboring no known genes, and provides evidence for a mode of gene expression autoregulation specific to the X chromosome. 相似文献