全文获取类型
收费全文 | 636篇 |
免费 | 51篇 |
出版年
2023年 | 3篇 |
2022年 | 5篇 |
2021年 | 18篇 |
2020年 | 6篇 |
2019年 | 14篇 |
2018年 | 13篇 |
2017年 | 13篇 |
2016年 | 12篇 |
2015年 | 27篇 |
2014年 | 36篇 |
2013年 | 34篇 |
2012年 | 44篇 |
2011年 | 62篇 |
2010年 | 24篇 |
2009年 | 25篇 |
2008年 | 40篇 |
2007年 | 33篇 |
2006年 | 39篇 |
2005年 | 32篇 |
2004年 | 24篇 |
2003年 | 22篇 |
2002年 | 27篇 |
2001年 | 14篇 |
2000年 | 16篇 |
1999年 | 12篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1971年 | 3篇 |
1968年 | 3篇 |
1966年 | 2篇 |
1965年 | 3篇 |
1964年 | 1篇 |
1962年 | 1篇 |
排序方式: 共有687条查询结果,搜索用时 62 毫秒
51.
Liu T Ortiz JA Taing L Meyer CA Lee B Zhang Y Shin H Wong SS Ma J Lei Y Pape UJ Poidinger M Chen Y Yeung K Brown M Turpaz Y Liu XS 《Genome biology》2011,12(8):R83-10
The increasing volume of ChIP-chip and ChIP-seq data being generated creates a challenge for standard, integrative and reproducible bioinformatics data analysis platforms. We developed a web-based application called Cistrome, based on the Galaxy open source framework. In addition to the standard Galaxy functions, Cistrome has 29 ChIP-chip- and ChIP-seq-specific tools in three major categories, from preliminary peak calling and correlation analyses to downstream genome feature association, gene expression analyses, and motif discovery. Cistrome is available at http://cistrome.org/ap/. 相似文献
52.
Oncolytic viruses (OVs) represent a relatively novel anti-cancer modality. Like other new cancer treatments, effective OV therapy will likely require combination with conventional treatments. In order to design combinatorial treatments that work well together, a greater scrutiny of the mechanisms behind the individual treatments is needed. Sindbis virus (SV) based vectors have previously been shown to target and kill tumors in xenograft, syngeneic, and spontaneous mouse models. However, the effect of SV treatment on the immune system has not yet been studied. Here we used a variety of methods, including FACS analysis, cytotoxicity assays, cell depletion, imaging of tumor growth, cytokine blockade, and survival experiments, to study how SV therapy affects Natural Killer (NK) cell function in SCID mice bearing human ovarian carcinoma tumors. Surprisingly, we found that SV anti-cancer efficacy is largely NK cell-dependent. Furthermore, the enhanced therapeutic effect previously observed from Sin/IL12 vectors, which carry the gene for interleukin 12, is also NK cell dependent, but works through a separate IFNγ-dependent mechanism, which also induces the activation of peritoneal macrophages. These results demonstrate the multimodular nature of SV therapy, and open up new possibilities for potential synergistic or additive combinatorial therapies with other treatments. 相似文献
53.
54.
55.
Reduction in interaction between cGMP and cAMP in dog ventricular myocytes with hypertrophic failure
Zhang Q Lazar M Molino B Rodriguez R Davidov T Su J Tse J Weiss HR Scholz PM 《American journal of physiology. Heart and circulatory physiology》2005,289(3):H1251-H1257
Baseline function and signal transduction are depressed in hearts with hypertrophic failure. We tested the hypothesis that the effects of cGMP and its interaction with cAMP would be reduced in cardiac myocytes from hypertrophic failing hearts. Ventricular myocytes were isolated from control dogs, dogs with aortic valve stenosis hypertrophy, and dogs with pacing hypertrophic failure. Myocyte function was measured using a video edge detector. Cell contraction data were obtained at baseline, with 8-bromo-cGMP (10(-7), 10(-6), and 10(-5) M), with erythro-9-(2-hydroxy-3-nonyl)adenine [EHNA; a cAMP phosphodiesterase (PDE(2)) inhibitor] plus 8-bromo-cGMP, or milrinone (a PDE(3) inhibitor) plus 8-bromo-cGMP. Baseline percent shortening and maximal rates of shortening (R(max)) and relaxation were slightly reduced in hypertrophic myocytes and were significantly lower in failing myocytes (R(max): control dogs, 95.3 +/- 17.3; hypertrophy dogs, 88.2 +/- 5.5; failure dogs, 53.2 +/- 6.4 mum/s). 8-Bromo-cGMP dose dependently reduced myocyte function in all groups. However, EHNA (10(-6) M) and milrinone (10(-6) M) significantly reduced the negative effects of cGMP on cell contractility in control and hypertrophy but not in failing myocytes (R(max) for control dogs: cGMP, -46%; +EHNA, -21%; +milrinone, -19%; for hypertrophy dogs: cGMP, -40%; +EHNA, -13%; +milrinone, -20%; for failure dogs: cGMP, -40%; +EHNA, -29%; +milrinone, -32%). Both combinations of EHNA-cGMP and milrinone-cGMP significantly increased intracellular cAMP in control, hypertrophic, and failing myocytes. These data indicated that the cGMP signaling pathway was preserved in hypertrophic failing cardiac myocytes. However, the interaction of cGMP with the cAMP signaling pathway was impaired in these failing myocytes. 相似文献
56.
A patient who developed an irregular sleep-wake pattern following prolactin-secreting pituitary microadenoma is described. The patient reported difficulties in sleep onset and awakening at the desired time, which caused major dysfunction in his daily life activities. Despite these difficulties, the sleep-related complaints of the patient remained unrecognized for as long as three yrs. Statistical analyses of the patient's rest-activity patterns revealed that the disruption of the sleep-wake circadian rhythm originated from a disharmony between ultradian (semicircadian) and circadian components. The circadian component displayed shorter than 24 h periodicity most of the time, but the semicircadian component fluctuated between longer and shorter than 12 h periods. Additionally, desynchrony in terms of period length was found in the tentative analyses of the rest-activity pattern, salivary melatonin, and oral temperature. While the salivary melatonin time series data could be characterized by a best-fit cosine curve of 24 h, the time series data of oral temperature was more compatible with 28 h best-fit curve. The rest-activity cycle during the simultaneous measurements, however, was best approximated by a best-fit curve of 21 h. The dysregulation of circadian rhythms occurred concomitantly, but not beforehand, with the onset of pituitary disease, thus suggesting an association between the two phenomena. This association may have interesting implications to the modeling of the circadian time-keeping system. This case also highlights the need to raise the awareness to circadian rhythm sleep disorders and to consider disruptions of sleep-wake cycle in patients with pituitary adenoma. 相似文献
57.
58.
Dynamics of transcription and mRNA export 总被引:1,自引:0,他引:1
59.
Kadiiska MB Gladen BC Baird DD Germolec D Graham LB Parker CE Nyska A Wachsman JT Ames BN Basu S Brot N Fitzgerald GA Floyd RA George M Heinecke JW Hatch GE Hensley K Lawson JA Marnett LJ Morrow JD Murray DM Plastaras J Roberts LJ Rokach J Shigenaga MK Sohal RS Sun J Tice RR Van Thiel DH Wellner D Walter PB Tomer KB Mason RP Barrett JC 《Free radical biology & medicine》2005,38(6):698-710
Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg i.p.) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects. 相似文献
60.
The class 3 Semaphorins Sema3A and Sema3F are potent axonal repellents that cause repulsion by binding Neuropilin-1 and Neuropilin-2, respectively. Plexins are implicated as signaling coreceptors for the Neuropilins, but the identity of the Plexins that transduce Sema3A and Sema3F responses in vivo is uncertain. Here, we show that Plexin-A3 and -A4 are key determinants of these responses, through analysis of a Plexin-A3/Plexin-A4 double mutant mouse. Sensory and sympathetic neurons from the double mutant are insensitive to Sema3A and Sema3F in vitro, and defects in axonal projections in vivo correspond to those seen in Neuropilin-1 and -2 mutants. Interestingly, we found a differential requirement for these two Plexins: signaling via Neuropilin-1 is mediated principally by Plexin-A4, whereas signaling via Neuropilin-2 is mediated principally by Plexin-A3. Thus, Plexin-A3 and -A4 contribute to the specificity of axonal responses to class 3 Semaphorins. 相似文献