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91.
Marie M Sannerud R Avsnes Dale H Saraste J 《Cellular and molecular life sciences : CMLS》2008,65(18):2859-2874
Cholesterol, certain lipids, membrane-bound and soluble proteins, as well as viruses that are synthesized in the endoplasmic reticulum (ER), reach the plasma membrane (PM) via non-classical pathway(s) that remain poorly understood. Typical for this transport is (i) its insensitivity to brefeldin A (BFA), which dissociates selected coat complexes from membranes, resulting in the disassembly of the Golgi apparatus; (ii) its rapid kinetics as compared to the classical secretory pathway; and (iii) its role in the trafficking of lipid raft components. Based on results showing that the intermediate compartment (IC) at the ER-Golgi boundary constitutes a stable tubular network that maintains its dynamics in the presence of BFA, we propose that two bidirectional Golgi-bypass pathways to the PM exist, a direct route from early IC elements, and another, reminiscent of the yeast secretory pathway, from late IC elements via the endosomal system. These pathways have implications for the organization of the secretory processes in different cell types. 相似文献
92.
Geneviève D Proulle V Isidor B Bellais S Serre V Djouadi F Picard C Vignon-Savoye C Bader-Meunier B Blanche S de Vernejoul MC Legeai-Mallet L Fischer AM Le Merrer M Dreyfus M Gaussem P Munnich A Cormier-Daire V 《Nature genetics》2008,40(3):284-286
Studying consanguineous families with Ghosal hematodiaphyseal dysplasia syndrome (GHDD), a disorder of increased bone density, we identified mutations in TBXAS1, which encodes thromboxane synthase (TXAS). TXAS, an enzyme of the arachidonic acid cascade, produces thromboxane A(2) (TXA(2)). Platelets from subjects with GHDD showed a specific deficit in arachidonic acid-produced aggregation. We also found that TXAS and TXA(2) modulated expression of TNFSF11 and TNFRSF11B (encoding RANKL and osteoprotegerin (OPG), respectively) in primary cultured osteoblasts. 相似文献
93.
A common approach to deal with missing values in multivariate exploratory data analysis consists in minimizing the loss function
over all non-missing elements, which can be achieved by EM-type algorithms where an iterative imputation of the missing values
is performed during the estimation of the axes and components. This paper proposes such an algorithm, named iterative multiple
correspondence analysis, to handle missing values in multiple correspondence analysis (MCA). The algorithm, based on an iterative
PCA algorithm, is described and its properties are studied. We point out the overfitting problem and propose a regularized
version of the algorithm to overcome this major issue. Finally, performances of the regularized iterative MCA algorithm (implemented in the R-package named missMDA) are assessed from both simulations and a real dataset. Results are
promising with respect to other methods such as the missing-data passive modified margin method, an adaptation of the missing passive method used in Gifi’s Homogeneity analysis framework. 相似文献
94.
Merveille AC Davis EE Becker-Heck A Legendre M Amirav I Bataille G Belmont J Beydon N Billen F Clément A Clercx C Coste A Crosbie R de Blic J Deleuze S Duquesnoy P Escalier D Escudier E Fliegauf M Horvath J Hill K Jorissen M Just J Kispert A Lathrop M Loges NT Marthin JK Momozawa Y Montantin G Nielsen KG Olbrich H Papon JF Rayet I Roger G Schmidts M Tenreiro H Towbin JA Zelenika D Zentgraf H Georges M Lequarré AS Katsanis N Omran H Amselem S 《Nature genetics》2011,43(1):72-78
Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex. 相似文献
95.
Putoux A Thomas S Coene KL Davis EE Alanay Y Ogur G Uz E Buzas D Gomes C Patrier S Bennett CL Elkhartoufi N Frison MH Rigonnot L Joyé N Pruvost S Utine GE Boduroglu K Nitschke P Fertitta L Thauvin-Robinet C Munnich A Cormier-Daire V Hennekam R Colin E Akarsu NA Bole-Feysot C Cagnard N Schmitt A Goudin N Lyonnet S Encha-Razavi F Siffroi JP Winey M Katsanis N Gonzales M Vekemans M Beales PL Attié-Bitach T 《Nature genetics》2011,43(6):601-606
96.
Marie Goulard Christine Dosquet Dominique Bonnet 《Cellular and molecular life sciences : CMLS》2018,75(8):1377-1391
The bone marrow microenvironment (BMM) regulates the fate of hematopoietic stem cells (HSCs) in homeostatic and pathologic conditions. In myeloid malignancies, new insights into the role of the BMM and its cellular and molecular actors in the progression of the diseases have started to emerge. In this review, we will focus on describing the major players of the HSC niche and the role of the altered niche function in myeloid malignancies, more specifically focusing on the mesenchymal stroma cell compartment. 相似文献
97.
Ludivine A. Pradelli Marie Bénéteau Jean-Ehrland Ricci 《Cellular and molecular life sciences : CMLS》2010,67(10):1589-1597
Mitochondria control whether a cell lives or dies. The role mitochondria play in deciding the fate of a cell was first identified
in the mid-1990s, because mitochondria-enriched fractions were found to be necessary for activation of death proteases, the
caspases, in a cell-free model of apoptotic cell death. Mitochondrial involvement in apoptosis was subsequently shown to be
regulated by Bcl-2, a protein that was known to contribute to cancer in specific circumstances. The important role of mitochondria
in promoting caspase activation has therefore been a major focus of apoptosis research; however, it is also clear that mitochondria
contribute to cell death by caspase-independent mechanisms. In this review, we will highlight recent findings and discuss
the mechanism underlying the mitochondrial control of apoptosis and caspase-independent cell death. 相似文献
98.
Delous M Baala L Salomon R Laclef C Vierkotten J Tory K Golzio C Lacoste T Besse L Ozilou C Moutkine I Hellman NE Anselme I Silbermann F Vesque C Gerhardt C Rattenberry E Wolf MT Gubler MC Martinovic J Encha-Razavi F Boddaert N Gonzales M Macher MA Nivet H Champion G Berthélémé JP Niaudet P McDonald F Hildebrandt F Johnson CA Vekemans M Antignac C Rüther U Schneider-Maunoury S Attié-Bitach T Saunier S 《Nature genetics》2007,39(7):875-881
Cerebello-oculo-renal syndrome (CORS), also called Joubert syndrome type B, and Meckel (MKS) syndrome belong to the group of developmental autosomal recessive disorders that are associated with primary cilium dysfunction. Using SNP mapping, we identified missense and truncating mutations in RPGRIP1L (KIAA1005) in both CORS and MKS, and we show that inactivation of the mouse ortholog Rpgrip1l (Ftm) recapitulates the cerebral, renal and hepatic defects of CORS and MKS. In addition, we show that RPGRIP1L colocalizes at the basal body and centrosomes with the protein products of both NPHP6 and NPHP4, known genes associated with MKS, CORS and nephronophthisis (a related renal disorder and ciliopathy). In addition, the RPGRIP1L missense mutations found in CORS individuals diminishes the interaction between RPGRIP1L and nephrocystin-4. Our findings show that mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in CORS or MKS, which therefore represent a continuum of the same underlying disorder. 相似文献
99.
Scheper GC van der Klok T van Andel RJ van Berkel CG Sissler M Smet J Muravina TI Serkov SV Uziel G Bugiani M Schiffmann R Krägeloh-Mann I Smeitink JA Florentz C Van Coster R Pronk JC van der Knaap MS 《Nature genetics》2007,39(4):534-539
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) has recently been defined based on a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. LBSL is an autosomal recessive disease, most often manifesting in early childhood. Affected individuals develop slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline. We performed linkage mapping with microsatellite markers in LBSL families and found a candidate region on chromosome 1, which we narrowed by means of shared haplotypes. Sequencing of genes in this candidate region uncovered mutations in DARS2, which encodes mitochondrial aspartyl-tRNA synthetase, in affected individuals from all 30 families. Enzyme activities of mutant proteins were decreased. We were surprised to find that activities of mitochondrial complexes from fibroblasts and lymphoblasts derived from affected individuals were normal, as determined by different assays. 相似文献
100.
Parma P Radi O Vidal V Chaboissier MC Dellambra E Valentini S Guerra L Schedl A Camerino G 《Nature genetics》2006,38(11):1304-1309
R-spondins are a recently characterized small family of growth factors. Here we show that human R-spondin1 (RSPO1) is the gene disrupted in a recessive syndrome characterized by XX sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Our data show, for the first time, that disruption of a single gene can lead to complete female-to-male sex reversal in the absence of the testis-determining gene, SRY. 相似文献