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排序方式: 共有513条查询结果,搜索用时 15 毫秒
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Ophir Shalem Lucas Carey Danny Zeevi Eilon Sharon Leeat Keren Adina Weinberger Orna Dahan Yitzhak Pilpel Eran Segal 《PLoS computational biology》2013,9(3)
A full understanding of gene regulation requires an understanding of the contributions that the various regulatory regions have on gene expression. Although it is well established that sequences downstream of the main promoter can affect expression, our understanding of the scale of this effect and how it is encoded in the DNA is limited. Here, to measure the effect of native S. cerevisiae 3′ end sequences on expression, we constructed a library of 85 fluorescent reporter strains that differ only in their 3′ end region. Notably, despite being driven by the same strong promoter, our library spans a continuous twelve-fold range of expression values. These measurements correlate with endogenous mRNA levels, suggesting that the 3′ end contributes to constitutive differences in mRNA levels. We used deep sequencing to map the 3′UTR ends of our strains and show that determination of polyadenylation sites is intrinsic to the local 3′ end sequence. Polyadenylation mapping was followed by sequence analysis, we found that increased A/T content upstream of the main polyadenylation site correlates with higher expression, both in the library and genome-wide, suggesting that native genes differ by the encoded efficiency of 3′ end processing. Finally, we use single cells fluorescence measurements, in different promoter activation levels, to show that 3′ end sequences modulate protein expression dynamics differently than promoters, by predominantly affecting the size of protein production bursts as opposed to the frequency at which these bursts occur. Altogether, our results lead to a more complete understanding of gene regulation by demonstrating that 3′ end regions have a unique and sequence dependent effect on gene expression. 相似文献
455.
Keren Kantarovich Inbal Tsarfati-BarAd Levi A. Gheber Karsten Haupt Ilana Bar 《Plasmonics (Norwell, Mass.)》2013,8(1):3-12
Biochips are a rapidly increasing research field, driven by the versatility of sensing devices and the importance of their applications. The regular approaches for creating biochips and for reading them suffer from some limitations, motivating development of miniature biochips and label-free formats. To push forward these challenges, we have chosen to combine the methods of printing of droplets of synthetic receptors by pipettes or nanofountain pens with detection by Raman spectroscopy or its surface-assisted plasmon variant, namely, surface-enhanced Raman spectroscopy (SERS). The selected receptors included molecularly imprinted polymers (MIPs), produced by polymerization of functional and cross-linking monomers around a molecular template, the β-blocking drug propranolol. The measured Raman and SERS spectra of the MIP constituents enabled identification of the template presence and consequently chemical imaging of individual and multiple dots in an array. This concept, combining nanolithography techniques with SERS paves the road toward miniaturized arrayed MIP sensors with label-free, specific and quantitative molecular recognition. 相似文献
456.
Keren Tazat Meirav Harsat Ayelet Goldshmid-Shagal Marcelo Ehrlich Yoav I. Henis 《Molecular biology of the cell》2013,24(11):1812-1824
Constitutive activation or overactivation of Ras signaling pathways contributes to epithelial tumorigenesis in several ways, one of which is cytoplasmic mislocalization of the cyclin-dependent kinase inhibitor p27Kip1 (p27). We previously showed that such an effect can be mediated by activation of the Ral-GEF pathway by oncogenic N-Ras. However, the mechanism(s) leading to p27 cytoplasmic accumulation downstream of activated Ral remained unknown. Here, we report a dual regulation of p27 cellular localization by Ral downstream pathways, based on opposing effects via the Ral effectors RalBP1 and phospholipase D1 (PLD1). Because RalA and RalB are equally effective in mislocalizing both murine and human p27, we focus on RalA and murine p27, which lacks the Thr-157 phosphorylation site of human p27. In experiments based on specific RalA and p27 mutants, complemented with short hairpin RNA–mediated knockdown of Ral downstream signaling components, we show that activation of RalBP1 induces cytoplasmic accumulation of p27 and that this event requires p27 Ser-10 phosphorylation by protein kinase B/Akt. Of note, activation of PLD1 counteracts this effect in a Ser-10–independent manner. The physiological relevance of the modulation of p27 localization by Ral is demonstrated by the ability of Ral-mediated activation of the RalBP1 pathway to abrogate transforming growth factor-β–mediated growth arrest in epithelial cells. 相似文献
457.
The Wnt signaling pathway is implicated in major physiologic cellular functions, such as proliferation, migration, cell fate specification, maintenance of pluripotency and induction of tumorigenicity. Proliferation and migration are important responses of T-cells, which are major cellular targets of HIV infection. Using an informatics screen, we identified a previously unsuspected interaction between HIV’s Nef protein and β-catenin, a key component of the Wnt pathway. A segment in Nef contains identical amino acids at key positions and structurally mimics the β-catenin binding sites on endogenous β-catenin ligands. The interaction between Nef and β-catenin was confirmed in vitro and in a co-immunoprecipitation from HEK293 cells. Moreover, the introduction of Nef into HEK293 cells specifically inhibited a Wnt pathway reporter. 相似文献
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Diurnal regulation of scent emission in rose flowers 总被引:3,自引:0,他引:3
Previous studies have shown diurnal oscillation of scent emission in rose flowers with a peak during the day (Helsper in Planta
207:88–95, 1998; Picone in Planta 219:468–478, 2004). Here, we studied the regulation of scent production and emission in
Rosa hybrida cv. Fragrant Cloud during the daily cycle and focused on two terpenoid compounds, germacrene D and geranyl acetate, whose
biosynthetic genes have been characterized by us previously. The emission of geranyl acetate oscillated during the daily light/dark
cycle with a peak early in the light period. A similar daily fluctuation was found in the endogenous level of this compound
and in the expression of its biosynthetic gene, alcohol acetyl transferase (RhAAT). The rhythmic expression of RhAAT continued under conditions of constant light or darkness, indicating regulation by the endogenous circadian clock. However,
the accumulation and emission of geranyl acetate ceased under continuous light. Our results suggest that geranyl acetate production
is limited by the level of its substrate geraniol, which is suppressed under constant light conditions. The emission of germacrene
D also oscillated during the daily cycle with a peak early in the light period. However, the endogenous level of this compound
and the expression of its biosynthetic gene germacrene D synthase (RhGDS) were constant throughout the day. The diurnal oscillation of germacrene D emission ceased under continuous light, suggesting
direct regulation by light. Our results demonstrate the complexity of the diurnal regulation of scent emission: although the
daily emission of most scent compounds is synchronized, various independently evolved mechanisms control the production, accumulation
and release of different volatiles.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
460.
Durst R Danenberg H Gallily R Mechoulam R Meir K Grad E Beeri R Pugatsch T Tarsish E Lotan C 《American journal of physiology. Heart and circulatory physiology》2007,293(6):H3602-H3607
Cannabidiol (CBD) is a major, nonpsychoactive Cannabis constituent with anti-inflammatory activity mediated by enhancing adenosine signaling. Inasmuch as adenosine receptors are promising pharmaceutical targets for ischemic heart diseases, we tested the effect of CBD on ischemic rat hearts. For the in vivo studies, the left anterior descending coronary artery was transiently ligated for 30 min, and the rats were treated for 7 days with CBD (5 mg/kg ip) or vehicle. Cardiac function was studied by echocardiography. Infarcts were examined morphometrically and histologically. For ex vivo evaluation, CBD was administered 24 and 1 h before the animals were killed, and hearts were harvested for physiological measurements. In vivo studies showed preservation of shortening fraction in CBD-treated animals: from 48 +/- 8 to 39 +/- 8% and from 44 +/- 5 to 32 +/- 9% in CBD-treated and control rats, respectively (n = 14, P < 0.05). Infarct size was reduced by 66% in CBD-treated animals, despite nearly identical areas at risk (9.6 +/- 3.9 and 28.2 +/- 7.0% in CBD and controls, respectively, P < 0.001) and granulation tissue proportion as assessed qualitatively. Infarcts in CBD-treated animals were associated with reduced myocardial inflammation and reduced IL-6 levels (254 +/- 22 and 2,812 +/- 500 pg/ml in CBD and control rats, respectively, P < 0.01). In isolated hearts, no significant difference in infarct size, left ventricular developed pressures during ischemia and reperfusion, or coronary flow could be detected between CBD-treated and control hearts. Our study shows that CBD induces a substantial in vivo cardioprotective effect from ischemia that is not observed ex vivo. Inasmuch as CBD has previously been administered to humans without causing side effects, it may represent a promising novel treatment for myocardial ischemia. 相似文献