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1.
The alpha-like globin gene cluster in rabbits contains embryonic zeta-
globin genes, an adult alpha-globin gene, and theta-globin genes of
undetermined function. The basic arrangement of genes, deduced from
analysis of cloned DNA fragments, is 5'-zeta 0-zeta 1-alpha 1-theta 1- zeta
2-zeta 3-theta 2-3'. However, the pattern of restriction fragments
containing zeta- and theta-globin genes varies among individual rabbits.
Analysis of BamHI fragments of genomic DNA from 24 New Zealand white
rabbits revealed eight different patterns of fragments containing
zeta-globin genes. The large BamHI fragments containing genes zeta 0 and
zeta 1 are polymorphic in length, whereas a 1.9-kb fragment containing the
zeta 2 gene and the 3.5-kb fragment containing the zeta 3 gene do not vary
in size. In contrast to this constancy in the size of the restriction
fragments, the copy number of the zeta 2 and zeta 3 genes does vary among
different rabbits. No length polymorphism was detected in the BamHI
fragments containing the theta-globin genes, but again the copy number
varies for restriction fragments containing the theta 2 gene. The alpha 1-
and theta 1-globin genes are located in a nonpolymorphic 7.2-kb BamHI
fragment. The combined data from hybridization with both zeta and theta
probes shows that the BamHI cleavage pattern does not vary within the
region 5'-alpha 1-theta 1- zeta 2-zeta 3-theta 2-3', but the pattern
genomic blot-hybridization patterns for the progeny of parental rabbits
with different zeta-globin gene patterns shows that the polymorphic
patterns are inherited in a Mendelian fashion. Two different haplotypes
have been mapped based on the genomic blot-hybridization data. The
variation in the alpha-like globin gene cluster in the rabbit population
results both from differences in the copy number of the duplication block
containing the zeta-zeta-theta gene set and from the presence or absence of
polymorphic BamHI sites.
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2.
Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium 总被引:13,自引:9,他引:4 下载免费PDF全文
Single batrachotoxin-activated sodium channels from rat brain were modified by trimethyloxonium (TMO) after incorporation in planar lipid bilayers. TMO modification eliminated saxitoxin (STX) sensitivity, reduced the single channel conductance by 37%, and reduced calcium block of inward sodium currents. These effects always occurred concomitantly, in an all-or-none fashion. Calcium and STX protected sodium channels from TMO modification with potencies similar to their affinities for block. Calcium inhibited STX binding to rat brain membrane vesicles and relieved toxin block of channels in bilayers, apparently by competing with STX for the toxin binding site. These results suggest that toxins, permeant cations, and blocking cations can interact with a common site on the sodium channel near the extracellular surface. It is likely that permeant cations transiently bind to this superficial site, as the first of several steps in passing inward through the channel. 相似文献
3.
Abstract Opportunistic sightings and strandings of Caperea marginata (n=196) from the vicinity of Australia and New Zealand (1884 to early 2007) were used to relate geographic and temporal patterns to oceanographic and broad-scale climatic variability. Records were not uniformly distributed along the coast and more (69%) were from Australia than New Zealand. Seven coastal whale ‘hotspots’ were identified which accounted for 61% of records with locality data. Half of the hotspot records were from southeast (37) and northwest (20) Tasmania—others each had 9–15 events. Upwelling and/or high zooplankton abundance has been documented near all whale hotspots. Records of C. marginata occurred in all months, with 75% in spring and summer. Inter-annual variability showed broad agreement between increased whale records (usually in spring/summer) and strongly positive ‘Niño 3.4’ during 1980–1995 but not thereafter. Coastal upwelling and productivity increase during climatic phenomena such as El Niño and are likely to be quickly beneficial to plankton-feeding whales such as C. marginata. 相似文献
4.
5.
Detection of biological toxins on an active electronic microchip 总被引:3,自引:0,他引:3
An electric-field-driven assay for fluorescein-labeled staphylococcal enterotoxin B and cholera toxin B was developed on an active electronic microchip. An array of microlocations was transformed into an immunoassay array by electronically biasing electrodes at each microlocation to attract biotinylated capture antibodies. The electric field generated on the array directed the transport, concentration, and binding of biotinylated capture antibodies to streptavidin-coated microlocations. Subsequently, solutions of fluorescein-labeled staphylococcal enterotoxin B and fluorescein-labeled cholera toxin B were electronically addressed to the assay sites by an applied electric field. Each toxin was specifically bound to microlocations containing the appropriate capture antibody with little nonspecific binding to assay sites lacking the appropriate capture antibody. It was possible to detect both toxins from a mixture in a single electronic addressing step; detection was accomplished after a 1-min application of the electric field followed by washing. The ability to perform a rapid, electric field-mediated immunoassay for multiple analytes may provide an advantage over existing approaches. 相似文献
6.
Margaret C. Ackley Colin G. Barry Amanda M. Mounce Michael C. Farmer Beth-Erin Springer Cynthia S. Day Marcus W. Wright Susan J. Berners-Price Suzanne M. Hess Ulrich Bierbach 《Journal of biological inorganic chemistry》2004,9(4):453-461
The synthesis, cytotoxicity, and nucleoside binding of some platinum–acridinylthiourea conjugates derived from the prototypical compound [PtCl(en)(ACRAMTU)](NO3)2 {PT-ACRAMTU; en=ethane-1,2-diamine, ACRAMTU=1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea, protonated form} are reported. To establish structure–activity relationships within this class of compounds, systematic changes were made to the thiourea nonleaving group, which links the intercalator to platinum. Three new derivatives of ACRAMTU, one di-, one tri-, and one tetraalkylated, were generated, where the degree of alkylation indicates the number of alkyl groups attached to the SCN2 framework. Subsequent reaction of the tri- and tetraalkylated derivatives with activated [PtCl2(en)] yielded the corresponding platinum conjugates. The dialkylated thiourea gave an unstable complex, which was not included in the studies. The crystal structure of PT-ACRAMTU·MeOH has been determined. In the solid state, one axial position of the square-planar platinum coordination sphere is partially shielded by the bulky thiourea group, providing a strong rationale for the kinetic inertness of the compound. The cytotoxicity of the prototype, the two new conjugates, and cisplatin was assessed in ovarian (A2780, A2780/CP), lung (NCI-H460), and colon (RKO) cancer cell lines using clonogenic survival assays. The derivatives containing trialkylated thiourea groups showed activity similar or superior to cisplatin, with IC50 values in the low micromolar concentration range. The complex modified with the tetraalkylated (bulkiest) thiourea was significantly less active, possibly due to the greatly decreased rate of binding to nucleobase nitrogen (1H NMR spectroscopy), but was most efficient at overcoming cross resistance to cisplatin in A2780/CP. Possible consequences of the reported structural modifications for the mechanism of action of these agents are discussed.Electronic Supplementary Material Supplementary material is available in the online version of this article at Abbreviations ACRAMTU 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea - Boc t-butyl carbamate - dGuo 2-deoxyguanosine - dien N1-(2-aminoethyl)ethane-1,2-diamine - en ethane-1,2-diamine - HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid - PT-ACRAMTU [PtCl(en)(ACRAMTU)](NO3)2 - TSP 3-(trimethylsilyl)propionate, sodium salt 相似文献
7.
Jolanda?HM?van Bilsen Josée?PA?Wagenaar-Hilbers Maarten?JF?van der Cammen Mariska?EA?van Dijk Willem?van Eden Marca?HM?WaubenEmail author 《Arthritis research & therapy》2002,4(4):R2
We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental
arthritis. In the present article, we investigate whether modulation of MMP-specific T-cell responses could influence the
course of adjuvant arthritis (AA). Lewis rats were treated nasally with MMP peptides prior to or after AA induction. Administration
of the MMP-10 or the MMP-16 peptide prior to AA induction reduced the arthritic symptoms. In contrast, administration of the
MMP-10 peptide after AA induction aggravated the arthritic symptoms. The present study shows the possible usefulness of MMP
peptides for immunotherapy. However, a clear understanding of proper timing of peptide administration is crucial for the development
of such therapies. 相似文献
8.
Papilin in development; a pericellular protein with a homology to the ADAMTS metalloproteinases 总被引:3,自引:0,他引:3
Kramerova IA Kawaguchi N Fessler LI Nelson RE Chen Y Kramerov AA Kusche-Gullberg M Kramer JM Ackley BD Sieron AL Prockop DJ Fessler JH 《Development (Cambridge, England)》2000,127(24):5475-5485
Papilin is an extracellular matrix glycoprotein that we have found to be involved in, (1) thin matrix layers during gastrulation, (2) matrix associated with wandering, phagocytic hemocytes, (3) basement membranes and (4) space-filling matrix during Drosophila development. Determination of its cDNA sequence led to the identification of Caenorhabditis and mammalian papilins. A distinctly conserved 'papilin cassette' of domains at the amino-end of papilins is also the carboxyl-end of the ADAMTS subgroup of secreted, matrix-associated metalloproteinases; this cassette contains one thrombospondin type 1 (TSR) domain, a specific cysteine-rich domain and several partial TSR domains. In vitro, papilin non-competitively inhibits procollagen N-proteinase, an ADAMTS metalloproteinase. Inhibiting papilin synthesis in Drosophila or Caenorhabditis causes defective cell arrangements and embryonic death. Ectopic expression of papilin in Drosophila causes lethal abnormalities in muscle, Malpighian tubule and trachea formation. We suggest that papilin influences cell rearrangements and may modulate metalloproteinases during organogenesis. 相似文献
9.
10.
Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia
Moreno-De-Luca D;SGENE Consortium Mulle JG;Simons Simplex Collection Genetics Consortium Kaminsky EB Sanders SJ;GeneSTAR Myers SM Adam MP Pakula AT Eisenhauer NJ Uhas K Weik L Guy L Care ME Morel CF Boni C Salbert BA Chandrareddy A Demmer LA Chow EW Surti U Aradhya S Pickering DL Golden DM Sanger WG Aston E Brothman AR Gliem TJ Thorland EC Ackley T Iyer R Huang S Barber JC Crolla JA Warren ST Martin CL Ledbetter DH 《American journal of human genetics》2010,87(5):618-630
Autism spectrum disorders (ASD) and schizophrenia are neurodevelopmental disorders for which recent evidence indicates an important etiologic role for rare copy number variants (CNVs) and suggests common genetic mechanisms. We performed cytogenomic array analysis in a discovery sample of patients with neurodevelopmental disorders referred for clinical testing. We detected a recurrent 1.4 Mb deletion at 17q12, which harbors HNF1B, the gene responsible for renal cysts and diabetes syndrome (RCAD), in 18/15,749 patients, including several with ASD, but 0/4,519 controls. We identified additional shared phenotypic features among nine patients available for clinical assessment, including macrocephaly, characteristic facial features, renal anomalies, and neurocognitive impairments. In a large follow-up sample, the same deletion was identified in 2/1,182 ASD/neurocognitive impairment and in 4/6,340 schizophrenia patients, but in 0/47,929 controls (corrected p = 7.37 × 10−5). These data demonstrate that deletion 17q12 is a recurrent, pathogenic CNV that confers a very high risk for ASD and schizophrenia and show that one or more of the 15 genes in the deleted interval is dosage sensitive and essential for normal brain development and function. In addition, the phenotypic features of patients with this CNV are consistent with a contiguous gene syndrome that extends beyond RCAD, which is caused by HNF1B mutations only. 相似文献