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排序方式: 共有140条查询结果,搜索用时 46 毫秒
41.
The first clinical gene delivery, which involved insertion of a marker gene into lymphocytes from cancer patients, was published 25 years ago. In this review, we describe progress since then in gene therapy. Patients with some inherited single-gene defects can now be treated with their own bone marrow stem cells that have been engineered with a viral vector carrying the missing gene. Patients with inherited retinopathies and haemophilia B can also be treated by local or systemic injection of viral vectors. There are also a number of promising gene therapy approaches for cancer and infectious disease. We predict that the next 25 years will see improvements in safety, efficacy and manufacture of gene delivery vectors and introduction of gene-editing technologies to the clinic. Gene delivery may also prove a cost-effective method for the delivery of biological medicines. 相似文献
42.
Zahid N. Rabbani Fawzia K Salahuddin Pavel Yarmolenko Ines Batinic-Haberle Bradley A. Thrasher Benjamin Gauter-Fleckenstein 《Free radical research》2013,47(11):1273-1282
The objective of this study was to determine whether administration of a catalytic antioxidant, Mn(III) tetrakis(N,N′-diethylimidazolium-2-yl) porphyrin, AEOL10150, reduces the severity of long-term lung injury induced by fractionated radiation (RT). Fisher 344 rats were randomized into five groups: RT+AEOL10150 (2.5 mg/kg BID), AEOL10150 (2.5 mg/kg BID) alone, RT+AEOL10150 (5 mg/kg BID), AEOL10150 (5 mg/kg BID) alone and RT alone. Animals received five 8 Gy fractions of RT to the right hemithorax. AEOL10150 was administered 15 min before RT and 8 h later during the period of RT treatment (5 days), followed by subcutaneous injections for 30 days, twice daily. Lung histology at 26 weeks revealed a significant decrease in lung structural damage and collagen deposition in RT+AEOL10150 (5 mg/kg BID) group, in comparison to RT alone. Immunohistochemistry studies revealed a significant reduction in tissue hypoxia (HIF1α, CAIX), angiogenic response (VEGF, CD-31), inflammation (ED-1), oxidative stress (8-OHdG, 3-nitrotyrosine) and fibrosis pathway (TGFβ1, Smad3, p-Smad2/3), in animals receiving RT+AEOL10150 (5 mg/kg BID). Administration of AEOL10150 at 5 mg/kg BID during and after RT results in a significant protective effect from long-term RT-induced lung injury. Low dose (2.5 mg/kg BID) delivery of AEOL10150 has no beneficial radioprotective effects. 相似文献
43.
Murine models of human genetic disorders provide a valuable tool for investigating the scope for application of induced pluripotent stem cells (iPSC). Here we present a proof-of-concept study to demonstrate generation of iPSC from a mouse model of X-linked chronic granulomatous disease (X-CGD), and their successful differentiation into haematopoietic progenitors of the myeloid lineage. We further demonstrate that additive gene transfer using lentiviral vectors encoding gp91(phox) is capable of restoring NADPH-oxidase activity in mature neutrophils derived from X-CGD iPSC. In the longer term, correction of iPSC from human patients with CGD has therapeutic potential not only through generation of transplantable haematopoietic stem cells, but also through production of large numbers of autologous functional neutrophils. 相似文献
44.
Himoudi N Nabarro S Yan M Gilmour K Thrasher AJ Anderson J 《Cancer immunology, immunotherapy : CII》2007,56(9):1381-1395
PAX3 is overexpressed in several human cancers and is absent from normal adult human tissues. It is known to have an oncogenic function in human malignancy, and is therefore a promising target for cancer immunotherapy. We screened the murine and human PAX3 amino acid sequences for peptides that bind common MHC class I types, and identified murine GVFINGRPL and human KLTEARVQV sequences. Mice immunised with either a selected PAX3 peptide, or with a PAX3 expressing DNA vector, developed specific anti-PAX3 immune responses that inhibited tumour growth. The intensity of the immune response was significantly enhanced by pulsing of the peptide onto dendritic cells. Anti-PAX3 T cell lines were established from splenocytes of immunised mice. Intravenous administration of anti-PAX3 T cells caused regression of established tumours indicating a promising clinical application for anti-PAX3 immunotherapy. The human peptide stimulated growth of similar T cell lines from peripheral blood of three out of three normal human blood donors. These showed specific cytotoxicity against a range of human PAX3+ and HLA-A2+ cancer cell lines. Moreover, an anti-PAX3 response was detected as a component of the anti-tumour immune response in a patient treated with lysate pulsed dendritic cell vaccination. The ability to generate strong and specific anti PAX3 immune responses from the T cell repertoire in both mice and humans, provides evidence for PAX3 as a promising target for immunotherapy of cancer. 相似文献
45.
Y Deng J Zhao D Sakurai KM Kaufman JC Edberg RP Kimberly DL Kamen GS Gilkeson CO Jacob RH Scofield CD Langefeld JA Kelly ME Alarcón-Riquelme BIOLUPUS GENLES Networks JB Harley TJ Vyse BI Freedman PM Gaffney KM Sivils JA James TB Niewold RM Cantor W Chen BH Hahn EE Brown PROFILE BP Tsao 《Arthritis research & therapy》2012,14(Z3):A5
46.
47.
Vidushi S Patel Steven JB Cooper Janine E Deakin Bob Fulton Tina Graves Wesley C Warren Richard K Wilson Jennifer AM Graves 《BMC biology》2008,6(1):34
Background
Vertebrate alpha (α)- and beta (β)-globin gene families exemplify the way in which genomes evolve to produce functional complexity. From tandem duplication of a single globin locus, the α- and β-globin clusters expanded, and then were separated onto different chromosomes. The previous finding of a fossil β-globin gene (ω) in the marsupial α-cluster, however, suggested that duplication of the α-β cluster onto two chromosomes, followed by lineage-specific gene loss and duplication, produced paralogous α- and β-globin clusters in birds and mammals. Here we analyse genomic data from an egg-laying monotreme mammal, the platypus (Ornithorhynchus anatinus), to explore haemoglobin evolution at the stem of the mammalian radiation. 相似文献48.
49.
Hierarchical analysis of variation in the mitochondrial 16S rRNA gene among Hymenoptera 总被引:5,自引:2,他引:3
Nucleotide sequences from a 434-bp region of the 16S rRNA gene were
analyzed for 65 taxa of Hymenoptera (ants, bees, wasps, parasitoid wasps,
sawflies) to examine the patterns of variation within the gene fragment and
the taxonomic levels for which it shows maximum utility in phylogeny
estimation. A hierarchical approach was adopted in the study through
comparison of levels of sequence variation among taxa at different
taxonomic levels. As previously reported for many holometabolous insects,
the 16S data reported here for Hymenoptera are highly AT-rich and exhibit
strong site-to-site variation in substitution rate. More precise estimates
of the shape parameter (alpha) of the gamma distribution and the proportion
of invariant sites were obtained in this study by employing a reference
phylogeny and utilizing maximum-likelihood estimation. The effectiveness of
this approach to recovering expected phylogenies of selected hymenopteran
taxa has been tested against the use of maximum parsimony. This study finds
that the 16S gene is most informative for phylogenetic analysis at two
different levels: among closely related species or populations, and among
tribes, subfamilies, and families. Maximization of the phylogenetic signal
extracted from the 16S gene at higher taxonomic levels may require
consideration of the base composition bias and the site-to-site rate
variation in a maximum-likelihood framework.
相似文献
50.
This report describes a convenient method for the rapid and efficient
release of N-linked oligosaccharides from low microgram amounts of
glycoproteins. A 96-well MultiScreen assay system containing a
polyvinylidene difluoride (PVDF) membrane is employed to immobilize
glycoproteins for subsequent enzymatic deglycosylation. Recombinant
tissue-type plasminogen activator (rt-PA) is used to demonstrate the
deglycosylation of 0.1-50 micrograms of a glycoprotein. This method enabled
the recovery of a sufficient amount of N-linked oligosaccharides released
enzymatically with peptide N-glycosidase F (PNGaseF) from as little as 0.5
microgram rt-PA for subsequent analysis by matrix-assisted laser
desorption/ionization time-of-flight (MALDI- TOF) mass spectrometry. The
immobilization of rt-PA to the PVDF membrane did not sterically inhibit the
PNGaseF-mediated release of oligosaccharides from rt-PA as determined by
tryptic mapping experiments. Comparison of the oligosaccharides released
from 50 micrograms of rt-PA by either the 96-well plate method or by a
standard solution digestion procedure showed no significant differences in
the profiles obtained by high-pH anion-exchange chromatography with pulsed
amperometric detection (HPAEC-PAD). Both neutral and sialylated
oligosaccharide standards spiked into wells were recovered equally as
determined by HPAEC-PAD. One advantage of this approach is that reduction
and alkylation can be performed on submicrogram amounts of glycoproteins
with easy removal of reagents prior to PNGaseF digestion. In addition, this
method allows 60 glycoprotein samples to be deglycosylated in 1 day with
MALDI-TOF or HPAEC-PAD analysis being performed on the following day.
相似文献