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71.
72.
Phillips GN Fox BG Markley JL Volkman BF Bae E Bitto E Bingman CA Frederick RO McCoy JG Lytle BL Pierce BS Song J Twigger SN 《Journal of structural and functional genomics》2007,8(2-3):73-84
The Center for Eukaryotic Structural Genomics (CESG) produces and solves the structures of proteins from eukaryotes. We have
developed and operate a pipeline to both solve structures and to test new methodologies. Both NMR and X-ray crystallography
methods are used for structure solution. CESG chooses targets based on sequence dissimilarity to known structures, medical
relevance, and nominations from members of the scientific community. Many times proteins qualify in more than one of these
categories. Here we review some of the structures that have connections to human health and disease. 相似文献
73.
Roeselers G Norris TB Castenholz RW Rysgaard S Glud RN Kühl M Muyzer G 《Environmental microbiology》2007,9(1):26-38
We investigated the genotypic diversity of oxygenic and anoxygenic phototrophic microorganisms in microbial mat samples collected from three hot spring localities on the east coast of Greenland. These hot springs harbour unique Arctic microbial ecosystems that have never been studied in detail before. Specific oligonucleotide primers for cyanobacteria, purple sulfur bacteria, green sulfur bacteria and Choroflexus/Roseiflexus-like green non-sulfur bacteria were used for the selective amplification of 16S rRNA gene fragments. Amplification products were separated by denaturing gradient gel electrophoresis (DGGE) and sequenced. In addition, several cyanobacteria were isolated from the mat samples, and classified morphologically and by 16S rRNA-based methods. The cyanobacterial 16S rRNA sequences obtained from DGGE represented a diverse, polyphyletic collection of cyanobacteria. The microbial mat communities were dominated by heterocystous and non-heterocystous filamentous cyanobacteria. Our results indicate that the cyanobacterial community composition in the samples were different for each sampling site. Different layers of the same heterogeneous mat often contained distinct and different communities of cyanobacteria. We observed a relationship between the cyanobacterial community composition and the in situ temperatures of different mat parts. The Greenland mats exhibited a low diversity of anoxygenic phototrophs as compared with other hot spring mats which is possibly related to the photochemical conditions within the mats resulting from the Arctic light regime. 相似文献
74.
75.
John L. Markley David J. Aceti Craig A. Bingman Brian G. Fox Ronnie O. Frederick Shin-ichi Makino Karl W. Nichols George N. Phillips Jr. John G. Primm Sarata C. Sahu Frank C. Vojtik Brian F. Volkman Russell L. Wrobel Zsolt Zolnai 《Journal of structural and functional genomics》2009,10(2):165-179
The Center for Eukaryotic Structural Genomics (CESG) is a “specialized” or “technology development” center supported by the
Protein Structure Initiative (PSI). CESG’s mission is to develop improved methods for the high-throughput solution of structures
from eukaryotic proteins, with a very strong weighting toward human proteins of biomedical relevance. During the first three
years of PSI-2, CESG selected targets representing 601 proteins from Homo sapiens, 33 from mouse, 10 from rat, 139 from Galdieria sulphuraria, 35 from Arabidopsis thaliana, 96 from Cyanidioschyzon merolae, 80 from Plasmodium falciparum, 24 from yeast, and about 25 from other eukaryotes. Notably, 30% of all structures of human proteins solved by the PSI Centers
were determined at CESG. Whereas eukaryotic proteins generally are considered to be much more challenging targets than prokaryotic
proteins, the technology now in place at CESG yields success rates that are comparable to those of the large production centers
that work primarily on prokaryotic proteins. We describe here the technological innovations that underlie CESG’s platforms
for bioinformatics and laboratory information management, target selection, protein production, and structure determination
by X-ray crystallography or NMR spectroscopy.
相似文献
John L. MarkleyEmail: |
76.
Neil Risch Shweta Choudhry Marc Via Analabha Basu Ronnie Sebro Celeste Eng Kenneth Beckman Shannon Thyne Rocio Chapela Jose R Rodriguez-Santana William Rodriguez-Cintron Pedro C Avila Elad Ziv Esteban Gonzalez Burchard 《Genome biology》2009,10(11):1-16
Background
While spouse correlations have been documented for numerous traits, no prior studies have assessed assortative mating for genetic ancestry in admixed populations.Results
Using 104 ancestry informative markers, we examined spouse correlations in genetic ancestry for Mexican spouse pairs recruited from Mexico City and the San Francisco Bay Area, and Puerto Rican spouse pairs recruited from Puerto Rico and New York City. In the Mexican pairs, we found strong spouse correlations for European and Native American ancestry, but no correlation in African ancestry. In the Puerto Rican pairs, we found significant spouse correlations for African ancestry and European ancestry but not Native American ancestry. Correlations were not attributable to variation in socioeconomic status or geographic heterogeneity. Past evidence of spouse correlation was also seen in the strong evidence of linkage disequilibrium between unlinked markers, which was accounted for in regression analysis by ancestral allele frequency difference at the pair of markers (European versus Native American for Mexicans, European versus African for Puerto Ricans). We also observed an excess of homozygosity at individual markers within the spouses, but this provided weaker evidence, as expected, of spouse correlation. Ancestry variance is predicted to decline in each generation, but less so under assortative mating. We used the current observed variances of ancestry to infer even stronger patterns of spouse ancestry correlation in previous generations.Conclusions
Assortative mating related to genetic ancestry persists in Latino populations to the current day, and has impacted on the genomic structure in these populations. 相似文献77.
Cadherin is an important cell adhesion molecule that plays paramount roles in organ development and the maintenance of tissue integrity. Dysregulation of cadherin expression is often associated with disease pathology including tissue dysplasia, tumor formation, and metastasis. Cadherin-17 (CDH17), belonging to a subclass of 7D-cadherin superfamily, is present in fetal liver and gastrointestinal tract during embryogenesis, but the gene becomes silenced in healthy adult liver and stomach tissues. It functions as a peptide transporter and a cell adhesion molecule to maintain tissue integrity in epithelia. However, recent findings from our group and others have reported aberrant expression of CDH17 in major gastrointestinal malignancies including hepatocellular carcinoma (HCC), stomach and colorectal cancers, and its clinical association with tumor metastasis and advanced tumor stages. Furthermore, alternative splice isoforms and genetic polymorphisms of CDH17 gene have been identified in HCC and linked to an increased risk of HCC. CDH17 is an attractive target for HCC therapy. Targeting CDH17 in HCC can inhibit tumor growth and inactivate Wnt signaling pathway in concomitance with activation of tumor suppressor genes. Further investigation on CDH17-mediated oncogenic signaling and cognate molecular mechanisms would shed light on new targeting therapy on HCC and potentially other gastrointestinal malignancies. 相似文献
78.
Delfien Syx Fransiska Malfait Lut Van Laer Jan Hellemans Trinh Hermanns-Lê Andy Willaert Abdelmajid Benmansour Anne De Paepe Alain Verloes 《Human genetics》2010,128(1):79-88
Defects leading to impaired intracellular trafficking have recently been shown to play an important role in the pathogenesis
of genodermatoses, such as the Ehlers–Danlos and the cutis laxa syndromes. A new genodermatosis, termed macrocephaly, alopecia,
cutis laxa and scoliosis (MACS) syndrome has been described, resulting from a homozygous 1-bp deletion in RIN2. RIN2 encodes the Ras and Rab interactor 2, involved in the regulation of Rab5-mediated early endocytosis. We performed a clinical,
ultrastructural and molecular study in a consanguineous Algerian family with three siblings affected by a distinctive autosomal
recessive genodermatosis, reported in 2005 by Verloes et al. The most striking clinical features include progressive facial
coarsening, gingival hypertrophy, severe scoliosis, sparse hair and skin and joint hyperlaxity. Ultrastructural studies of
the skin revealed important abnormalities in the collagen fibril morphology, and fibroblasts exhibited a dilated endoplasmic
reticulum and an abnormal Golgi apparatus with rarefied and dilated cisternae. Molecular analysis of RIN2 revealed a novel homozygous 2-bp deletion in all affected individuals. The c.1914_1915delGC mutation introduces a frameshift
and creates a premature termination codon, leading to nonsense-mediated mRNA decay. These findings confirm that RIN2 defects are associated with a distinct genodermatosis and underscore the involvement of RIN2 and its associated pathways in the pathogenesis of connective tissue disorders. The current family displays considerable
phenotypic overlap with MACS syndrome. However, our family shows a dermatological and ultrastructural phenotype belonging
to the Ehlers–Danlos rather than the cutis laxa spectrum. Therefore, the MACS acronym is not entirely appropriate for the
current family. 相似文献
79.
Haofan Wang Youngjoo Byun Cyril Barinka Mrudula Pullambhatla Hyo-eun C. Bhang James J. Fox Jacek Lubkowski Ronnie C. Mease Martin G. Pomper 《Bioorganic & medicinal chemistry letters》2010,20(1):392-397
We report a strategy based on bioisosterism to improve the physicochemical properties of existing hydrophilic, urea-based GCPII inhibitors. Comprehensive structure–activity relationship studies of the P1′ site of ZJ-43- and DCIBzL-based compounds identified several glutamate-free inhibitors with Ki values below 20 nM. Among them, compound 32d (Ki = 11 nM) exhibited selective uptake in GCPII-expressing tumors by SPECT-CT imaging in mice. A novel conformational change of amino acids in the S1′ pharmacophore pocket was observed in the X-ray crystal structure of GCPII complexed with 32d. 相似文献
80.
Standardized reagents and protocols for engineering zinc finger nucleases by modular assembly 总被引:1,自引:0,他引:1
Wright DA Thibodeau-Beganny S Sander JD Winfrey RJ Hirsh AS Eichtinger M Fu F Porteus MH Dobbs D Voytas DF Joung JK 《Nature protocols》2006,1(3):1637-1652
Engineered zinc finger nucleases can stimulate gene targeting at specific genomic loci in insect, plant and human cells. Although several platforms for constructing artificial zinc finger arrays using "modular assembly" have been described, standardized reagents and protocols that permit rapid, cross-platform "mixing-and-matching" of the various zinc finger modules are not available. Here we describe a comprehensive, publicly available archive of plasmids encoding more than 140 well-characterized zinc finger modules together with complementary web-based software (termed ZiFiT) for identifying potential zinc finger target sites in a gene of interest. Our reagents have been standardized on a single platform, enabling facile mixing-and-matching of modules and transfer of assembled arrays to expression vectors without the need for specialized knowledge of zinc finger sequences or complicated oligonucleotide design. We also describe a bacterial cell-based reporter assay for rapidly screening the DNA-binding activities of assembled multi-finger arrays. This protocol can be completed in approximately 24-26 d. 相似文献