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121.
122.
The genome of woodland strawberry (Fragaria vesca) 总被引:3,自引:0,他引:3
Shulaev V Sargent DJ Crowhurst RN Mockler TC Folkerts O Delcher AL Jaiswal P Mockaitis K Liston A Mane SP Burns P Davis TM Slovin JP Bassil N Hellens RP Evans C Harkins T Kodira C Desany B Crasta OR Jensen RV Allan AC Michael TP Setubal JC Celton JM Rees DJ Williams KP Holt SH Ruiz Rojas JJ Chatterjee M Liu B Silva H Meisel L Adato A Filichkin SA Troggio M Viola R Ashman TL Wang H Dharmawardhana P Elser J Raja R Priest HD Bryant DW Fox SE Givan SA Wilhelm LJ Naithani S Christoffels A Salama DY 《Nature genetics》2011,43(2):109-116
123.
Smith UM Consugar M Tee LJ McKee BM Maina EN Whelan S Morgan NV Goranson E Gissen P Lilliquist S Aligianis IA Ward CJ Pasha S Punyashthiti R Malik Sharif S Batman PA Bennett CP Woods CG McKeown C Bucourt M Miller CA Cox P Algazali L Trembath RC Torres VE Attie-Bitach T Kelly DA Maher ER Gattone VH Harris PC Johnson CA 《Nature genetics》2006,38(2):191-196
Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system (most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995-amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin. 相似文献
124.
Therapeutic strategies to ameliorate lysosomal storage disorders – a focus on Gaucher disease 总被引:4,自引:0,他引:4
The lysosomal storage disorders encompass more than 40 distinct diseases, most of which are caused by the deficient activity
of a lysosomal hydrolase leading to the progressive, intralysosomal accumulation of substrates such as sphingolipids, mucopolysaccharides,
and oligosaccharides. Here, we primarily focus on Gaucher disease, one of the most prevalent lysosomal storage disorders,
which is caused by an impaired activity of glucocerebrosidase, resulting in the accumulation of the glycosphingolipid glucosylceramide
in the lysosomes. Enzyme replacement and substrate reduction therapies have proven effective for Gaucher disease cases without
central nervous system involvement. We discuss the promise of chemical chaperone therapy to complement established therapeutic
strategies for Gaucher disease. Chemical chaperones are small molecules that bind to the active site of glucocerebrosidase
variants stabilizing their threedimensional structure in the endoplasmic reticulum, likely preventing their endoplasmic reticulum-associated
degradation and allowing their proper trafficking to the lysosome where they can degrade accumulated substrate to effectively
ameliorate Gaucher disease.
Received 22 September 2005; received after revision 15 December 2006; accepted 2 February 2006 相似文献
125.
Mollie L. Kelly Artyom Astsaturov Jonathan Chernoff 《Cellular and molecular life sciences : CMLS》2013,70(22):4223-4228
p21-activated kinases (Paks) are a group of six serine/threonine kinases (Pak1-6) that are involved in a variety of biological processes. Recently, Paks, more specifically Pak1, -2, and -4, have been shown to play important roles in cardiovascular development and function in a range of model organisms including zebrafish and mice. These functions include proper morphogenesis and conductance of the heart, cardiac contractility, and development and integrity of the vasculature. The mechanisms underlying these effects are not fully known, but they likely differ among the various Pak isoforms and include both kinase-dependent and -independent functions. In this review, we discuss aspects of Pak function relevant to cardiovascular biology as well as potential therapeutic implications of small-molecule Pak inhibitors in cardiovascular disease. 相似文献
126.
A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures 总被引:1,自引:0,他引:1
Sharp AJ Mefford HC Li K Baker C Skinner C Stevenson RE Schroer RJ Novara F De Gregori M Ciccone R Broomer A Casuga I Wang Y Xiao C Barbacioru C Gimelli G Bernardina BD Torniero C Giorda R Regan R Murday V Mansour S Fichera M Castiglia L Failla P Ventura M Jiang Z Cooper GM Knight SJ Romano C Zuffardi O Chen C Schwartz CE Eichler EE 《Nature genetics》2008,40(3):322-328
We report a recurrent microdeletion syndrome causing mental retardation, epilepsy and variable facial and digital dysmorphisms. We describe nine affected individuals, including six probands: two with de novo deletions, two who inherited the deletion from an affected parent and two with unknown inheritance. The proximal breakpoint of the largest deletion is contiguous with breakpoint 3 (BP3) of the Prader-Willi and Angelman syndrome region, extending 3.95 Mb distally to BP5. A smaller 1.5-Mb deletion has a proximal breakpoint within the larger deletion (BP4) and shares the same distal BP5. This recurrent 1.5-Mb deletion contains six genes, including a candidate gene for epilepsy (CHRNA7) that is probably responsible for the observed seizure phenotype. The BP4-BP5 region undergoes frequent inversion, suggesting a possible link between this inversion polymorphism and recurrent deletion. The frequency of these microdeletions in mental retardation cases is approximately 0.3% (6/2,082 tested), a prevalence comparable to that of Williams, Angelman and Prader-Willi syndromes. 相似文献
127.
128.
McGowan KA Li JZ Park CY Beaudry V Tabor HK Sabnis AJ Zhang W Fuchs H de Angelis MH Myers RM Attardi LD Barsh GS 《Nature genetics》2008,40(8):963-970
Mutations in genes encoding ribosomal proteins cause the Minute phenotype in Drosophila and mice, and Diamond-Blackfan syndrome in humans. Here we report two mouse dark skin (Dsk) loci caused by mutations in Rps19 (ribosomal protein S19) and Rps20 (ribosomal protein S20). We identify a common pathophysiologic program in which p53 stabilization stimulates Kit ligand expression, and, consequently, epidermal melanocytosis via a paracrine mechanism. Accumulation of p53 also causes reduced body size and erythrocyte count. These results provide a mechanistic explanation for the diverse collection of phenotypes that accompany reduced dosage of genes encoding ribosomal proteins, and have implications for understanding normal human variation and human disease. 相似文献
129.
Tarpey PS Raymond FL Nguyen LS Rodriguez J Hackett A Vandeleur L Smith R Shoubridge C Edkins S Stevens C O'Meara S Tofts C Barthorpe S Buck G Cole J Halliday K Hills K Jones D Mironenko T Perry J Varian J West S Widaa S Teague J Dicks E Butler A Menzies A Richardson D Jenkinson A Shepherd R Raine K Moon J Luo Y Parnau J Bhat SS Gardner A Corbett M Brooks D Thomas P Parkinson-Lawrence E Porteous ME Warner JP Sanderson T Pearson P Simensen RJ Skinner C Hoganson G Superneau D Wooster R Bobrow M 《Nature genetics》2007,39(9):1127-1133
130.
New models of collaboration in genome-wide association studies: the Genetic Association Information Network 总被引:7,自引:0,他引:7
GAIN Collaborative Research Group Manolio TA Rodriguez LL Brooks L Abecasis G;Collaborative Association Study of Psoriasis Ballinger D Daly M Donnelly P Faraone SV;International Multi-Center ADHD Genetics Project Frazer K Gabriel S Gejman P;Molecular Genetics of Schizophrenia Collaboration Guttmacher A Harris EL Insel T Kelsoe JR;Bipolar Genome Study Lander E McCowin N Mailman MD Nabel E Ostell J Pugh E Sherry S 《Nature genetics》2007,39(9):1045-1051
The Genetic Association Information Network (GAIN) is a public-private partnership established to investigate the genetic basis of common diseases through a series of collaborative genome-wide association studies. GAIN has used new approaches for project selection, data deposition and distribution, collaborative analysis, publication and protection from premature intellectual property claims. These demonstrate a new commitment to shared scientific knowledge that should facilitate rapid advances in understanding the genetics of complex diseases. 相似文献