全文获取类型
收费全文 | 572篇 |
免费 | 99篇 |
出版年
2021年 | 8篇 |
2019年 | 4篇 |
2017年 | 4篇 |
2016年 | 10篇 |
2015年 | 22篇 |
2014年 | 13篇 |
2013年 | 21篇 |
2012年 | 33篇 |
2011年 | 27篇 |
2010年 | 21篇 |
2009年 | 17篇 |
2008年 | 21篇 |
2007年 | 20篇 |
2006年 | 29篇 |
2005年 | 16篇 |
2004年 | 25篇 |
2003年 | 12篇 |
2002年 | 24篇 |
2001年 | 14篇 |
2000年 | 18篇 |
1999年 | 21篇 |
1998年 | 8篇 |
1997年 | 10篇 |
1996年 | 10篇 |
1995年 | 9篇 |
1994年 | 5篇 |
1993年 | 9篇 |
1992年 | 12篇 |
1991年 | 13篇 |
1990年 | 12篇 |
1989年 | 14篇 |
1988年 | 16篇 |
1987年 | 9篇 |
1986年 | 10篇 |
1985年 | 12篇 |
1984年 | 4篇 |
1983年 | 15篇 |
1982年 | 8篇 |
1980年 | 8篇 |
1979年 | 14篇 |
1978年 | 9篇 |
1977年 | 10篇 |
1976年 | 4篇 |
1975年 | 7篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1967年 | 6篇 |
1966年 | 7篇 |
1961年 | 5篇 |
1958年 | 3篇 |
排序方式: 共有671条查询结果,搜索用时 453 毫秒
81.
Asdaghi N Kilani RT Hosseini-Tabatabaei A Odemuyiwa SO Hackett TL Knight DA Ghahary A Moqbel R 《Molecular and cellular biochemistry》2012,360(1-2):261-270
Airway remodelling in asthma involves various mediators modulating the production/breakdown of collagen by lung fibroblasts. Matrix metalloproteinase-1 (MMP-1) plays an important role in collagen breakdown. We recently showed that epithelial cell-derived extracellular form of 14-3-3σ is an important inducer of MMP-1 expression in skin fibroblasts. Thus, we hypothesized that 14-3-3 proteins are important regulators of MMP-1 expression in the respiratory airway. We examined the presence of extracellular 14-3-3 proteins in conditioned media obtained from primary lung epithelial cells, A549 and HS24 cells, and their effect on MMP-1 expression by lung fibroblasts (IMR-90). In addition, we evaluated IMR-90 response to 14-3-3 proteins in the presence of transforming growth factor-β(1) (TGF-β(1)), a cytokine known to decrease MMP-1 expression by fibroblasts. Extracellular 14-3-3α/β, but not -σ, is released by the human-derived lung epithelial cell lines, A549 and HS24. Unlike dermal fibroblasts, IMR-90 cells do not produce MMP-1 in response to 14-3-3σ. Conversely, MMP-1 production was induced following treatment of IMR-90 with recombinant or lung epithelial cell-derived 14-3-3α/β. These findings were also confirmed using primary human bronchial epithelial cells and lung fibroblasts obtained from non-asthmatic patients. The MMP-1-inducing effect of 14-3-3α/β on IMR-90 was not inhibited by TGF-β(1). Lung epithelial cell-derived 14-3-3α/β has a potent MMP-1-inducing effect on airway fibroblasts. Modulation of MMP-1 by 14-3-3α/β, may be important in the alteration of collagenase production associated with airway remodelling in obstructive lung diseases. Our data indicate that 14-3-3 proteins may be potential targets for future therapeutic strategies aimed at modulating tissue remodelling in asthma. 相似文献
82.
JA Hackett JP Reddington CE Nestor DS Dunican MR Branco J Reichmann W Reik MA Surani IR Adams RR Meehan 《Development (Cambridge, England)》2012,139(19):3623-3632
Mouse primordial germ cells (PGCs) erase global DNA methylation (5mC) as part of the comprehensive epigenetic reprogramming that occurs during PGC development. 5mC plays an important role in maintaining stable gene silencing and repression of transposable elements (TE) but it is not clear how the extensive loss of DNA methylation impacts on gene expression and TE repression in developing PGCs. Using a novel epigenetic disruption and recovery screen and genetic analyses, we identified a core set of germline-specific genes that are dependent exclusively on promoter DNA methylation for initiation and maintenance of developmental silencing. These gene promoters appear to possess a specialised chromatin environment that does not acquire any of the repressive H3K27me3, H3K9me2, H3K9me3 or H4K20me3 histone modifications when silenced by DNA methylation. Intriguingly, this methylation-dependent subset is highly enriched in genes with roles in suppressing TE activity in germ cells. We show that the mechanism for developmental regulation of the germline genome-defence genes involves DNMT3B-dependent de novo DNA methylation. These genes are then activated by lineage-specific promoter demethylation during distinct global epigenetic reprogramming events in migratory (~E8.5) and post-migratory (E10.5-11.5) PGCs. We propose that genes involved in genome defence are developmentally regulated primarily by promoter DNA methylation as a sensory mechanism that is coupled to the potential for TE activation during global 5mC erasure, thereby acting as a failsafe to ensure TE suppression and maintain genomic integrity in the germline. 相似文献
83.
84.
QTL mapping of yield, agronomic and quality traits in tetraploid potato (Solanum tuberosum subsp. tuberosum) 总被引:2,自引:0,他引:2
Bradshaw JE Hackett CA Pande B Waugh R Bryan GJ 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2008,116(2):193-211
Interval mapping of quantitative trait loci (QTL) for 16 yield, agronomic and quality traits in potato was performed on a
tetraploid full-sib family comprising 227 clones from a cross between processing clone 12601ab1 and table cultivar Stirling.
Thirty-eight AFLP primer combinations and six SSRs provided 514 informative markers which formed a molecular marker map comprising
12 linkage groups (LGs) in 12601ab1 (nine with four homologous chromosomes) which were aligned with 12 in Stirling (11 with
four homologous chromosomes), with four partial groups remaining in 12601ab1. Two LGs were identified unequivocally as chromosomes
IV and V and eight others were tentatively assigned with chromosomes VII and X unidentified. All of the traits scored had
moderately high heritabilities with 54–92% of the variation in clone means over 3 years and two replicates being due to genetic
differences. A total of 39 QTLs were identified. A QTL for maturity was identified on chromosome V which explained 56% of
the phenotypic variance, whereas the other QTLs individually explained between 5.4 and 16.5%. However, six QTLs were detected
for after-cooking blackening and four for each of regularity of tuber shape, fry colour both after storage at 4 and 10°C and
sprouting. Just two QTLs were found for each of yield, the two ‘overall’ scores, crop emergence, tuber size and common scab
and just one QTL was detected for each of dry matter content, keeping quality, growth cracks and internal condition. The implications
for practical potato breeding and for practical linkage and QTL analysis in autotetraploids are discussed. 相似文献
85.
86.
Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. 总被引:73,自引:0,他引:73
D Lyden K Hattori S Dias C Costa P Blaikie L Butros A Chadburn B Heissig W Marks L Witte Y Wu D Hicklin Z Zhu N R Hackett R G Crystal M A Moore K A Hajjar K Manova R Benezra S Rafii 《Nature medicine》2001,7(11):1194-1201
The role of bone marrow (BM)-derived precursor cells in tumor angiogenesis is not known. We demonstrate here that tumor angiogenesis is associated with recruitment of hematopoietic and circulating endothelial precursor cells (CEPs). We used the angiogenic defective, tumor resistant Id-mutant mice to show that transplantation of wild-type BM or vascular endothelial growth factor (VEGF)-mobilized stem cells restore tumor angiogenesis and growth. We detected donor-derived CEPs throughout the neovessels of tumors and Matrigel-plugs in an Id1+/-Id3-/- host, which were associated with VEGF-receptor-1-positive (VEGFR1+) myeloid cells. The angiogenic defect in Id-mutant mice was due to impaired VEGF-driven mobilization of VEGFR2+ CEPs and impaired proliferation and incorporation of VEGFR1+ cells. Although targeting of either VEGFR1 or VEGFR2 alone partially blocks the growth of tumors, inhibition of both VEGFR1 and VEGFR2 was necessary to completely ablate tumor growth. These data demonstrate that recruitment of VEGF-responsive BM-derived precursors is necessary and sufficient for tumor angiogenesis and suggest new clinical strategies to block tumor growth. 相似文献
87.
Maree L Hackett Nicholas S Glozier Alexandra L Martiniuk Stephen Jan Craig S Anderson 《BMC neurology》2011,11(1):3
Background
Epilepsy affects an estimated 50 million people and accounts for approximately 1% of days lost to ill health globally, making it one of the most common, serious neurological disorders. While there are abundant global data on epilepsy incidence, prevalence and treatment, there is a paucity of Australian incidence data. There is also a general lack of information on the psychosocial impact and socioeconomic consequences of a new diagnosis of epilepsy on an individual, their family, household, and community which are often specific to the health and social system of each country. 相似文献88.
89.
Lili Lu Christopher P. Seidel Takeshi Iwase Rebecca K. Stevens Yuan‐Yuan Gong Xinyi Wang Sean F. Hackett Peter A. Campochiaro 《Journal of cellular physiology》2013,228(2):251-257
High blood glucose results in high glucose levels in retina, because GLUT1, the sole glucose transporter between blood and retina, transports more glucose when blood glucose is high. This is the ultimate cause of diabetic retinopathy. Knockdown of GLUT1 by intraocular injections of a pool of siRNAs directed against SLC2A1 mRNA which codes for GLUT1 significantly reduced mean retinal glucose levels in diabetic mice. Systemic treatment of diabetic mice with forskolin or genistein, which bind GLUT1 and inhibit glucose transport, significantly reduced retinal glucose to the same levels seen in non‐diabetics. 1,9‐Dideoxyforskolin, which binds GLUT1 but does not stimulate adenylate cyclase had an equivalent effect to that of forskolin regarding lowering retinal glucose in diabetics indicating that cyclic AMP is noncontributory. GLUT1 inhibitors also reduced glucose and glycohemoglobin levels in red blood cells providing a peripheral biomarker for the effect. In contrast, brain glucose levels were not increased in diabetics and not reduced by forskolin. Treatment of diabetics with forskolin prevented early biomarkers of diabetic retinopathy, including elevation of superoxide radicals, increased expression of the chaperone protein β2 crystallin, and increased expression of vascular endothelial growth factor (VEGF). These data identify GLUT1 as a promising therapeutic target for prevention of diabetic retinopathy. J. Cell. Physiol. 228: 251–257, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
90.
Robert F. Whitcomb Frank E. French Joseph G. Tully Patricia Carle Roberta Henegar Kevin J. Hackett Gail E. Gasparich David L. Williamson 《Current microbiology》1997,35(5):287-293
Twenty-one triply cloned spiroplasma strains from the United States east of the Rocky Mountains, all isolated from tabanid
(Diptera:Tabanidae) flies or serologically related to strains from tabanids, were compared reciprocally by spiroplasma deformation
(DF) and metabolism inhibition (MI) serological tests. Many of the strains were also tested against 28 antisera representing
known spiroplasma groups, subgroups, and putative groups isolated from nontabanid hosts. Relationships among strains were
indicated by reciprocal cross-reactivity in both DF and MI tests. The strains were found to represent 11 recognized spiroplasma
groups or subgroups. On the basis of serological, biochemical, and genomic data, strain BARC 1901 from Tabanus lineola appeared to represent a previously unrecognized candidate group. Strain BARC 2649, also from T. lineola, also appeared to represent a new group, but its morphology, arginine utilization, and some one-way serological crossing
patterns suggested that it may be distantly related to group VIII spiroplasmas. Morphological, serological, and genomic data
were used to place tabanid spiroplasma strains into three informal clusters. These are (i) groups IV (strain B31) and XXXI
(strain HYOS-1); (ii) the three existing subgroups and a new candidate subgroup of group VIII represented by strain BARC 1357
plus ungrouped strain BARC 2649; and (iii) 14 strains, including EC-1 and TATS-1 (group XIV); strains TN-1 and TAAS-2 (group
XVIII); strains TG-1, TASS-1, and BARC 4689 (group XXIII), strains TALS-2 (group XXVII), strain TABS-2 (group XXXII), and
strains TAUS-1 and TABS-1 (group XXXIII) and ungrouped but closely related strains BARC 1901, BARC 2264 and BARC 2555. Analysis
of tabanids from other geographic regions probably will substantially increase the number of known spiroplasma groups from
this insect family.
Received: 23 April 1997 / Accepted: 31 May 1997 相似文献