全文获取类型
收费全文 | 201篇 |
免费 | 11篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 1篇 |
2017年 | 5篇 |
2016年 | 12篇 |
2015年 | 19篇 |
2014年 | 14篇 |
2013年 | 20篇 |
2012年 | 16篇 |
2011年 | 11篇 |
2010年 | 8篇 |
2009年 | 6篇 |
2008年 | 8篇 |
2007年 | 9篇 |
2006年 | 6篇 |
2005年 | 13篇 |
2004年 | 3篇 |
2003年 | 12篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1991年 | 2篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有212条查询结果,搜索用时 2 毫秒
81.
Carolyn Roitsch Tilman Achstetter Miloud Benchaibi Edwige Bonfils Gilles Cauet Remi Gloeckler Herve Lhte Elisabeth Keppi Martine Nguyen Daniele Spehner Alain Van Dorsselaer Daniel Malarme 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2001,752(2):263-280
Highly purified recombinant adenovirus undergoes routine quality controls for identity, potency and purity prior to its use as a gene therapy vector. Quantitative characterization of infectivity is measurable by the expression of the DNA binding protein, an early adenoviral protein, in an immunofluorescence bioassay on permissive cells as a potency determinant. The specific particle count, a key quality indicator, is the total number of intact particles present compared to the number of infectious units. Electron microscopic analysis using negative staining gives a qualitative biophysical analysis of the particles eluted from anion-exchange HPLC. One purity assessment is accomplished via the documented presence and relative ratios of component adenoviral proteins as well as potential contaminants by reversed-phase HPLC of the intact virus followed by protein peak identification using MALDI-TOF mass spectrometry and subsequent data mining. Verification of the viral genome is performed and expression of the transgene is evaluated in in vitro systems for identity. Production lots are also evaluated for replication-competent adenovirus prior to human use. For adenovirus carrying the human IL-2 transgene, quantitative IL-2 expression is demonstrated by ELISA and cytokine potency by cytotoxic T lymphocyte assay following infection of permissive cells. Both quantitative and qualitative analyses show good batch to batch reproducibility under routine test conditions using validated methods. 相似文献
82.
Tomasz Rewicz Remi Wattier Thierry Rigaud Michał Grabowski Tomasz Mamos Karolina Bącela‐Spychalska 《Freshwater Biology》2017,62(6):1036-1051
- 相似文献
83.
84.
Flavio Ronzoni Thibaud Magouroux Remi Vernet Jér?me Extermann Darragh Crotty Adriele Prina-Mello Daniel Ciepielewski Yuri Volkov Luigi Bonacina Jean-Pierre Wolf Marisa Jaconi 《Journal of visualized experiments : JoVE》2014,(87)
In this visualized experiment, protocol details are provided for in vitro labeling of human embryonic stem cells (hESC) with second harmonic generation nanoparticles (HNPs). The latter are a new family of probes recently introduced for labeling biological samples for multi-photon imaging. HNPs are capable of doubling the frequency of excitation light by the nonlinear optical process of second harmonic generation with no restriction on the excitation wavelength.Multi-photon based methodologies for hESC differentiation into cardiac clusters (maintained as long term air-liquid cultures) are presented in detail. In particular, evidence on how to maximize the intense second harmonic (SH) emission of isolated HNPs during 3D monitoring of beating cardiac tissue in 3D is shown. The analysis of the resulting images to retrieve 3D displacement patterns is also detailed. 相似文献
85.
Tomasz Mamos Remi Wattier Aneta Majda Boris Sket Micha Grabowski 《Journal of Zoological Systematics and Evolutionary Research》2014,52(3):237-248
Mountainous areas are characterized by substantial biodiversity and endemicity due to their complex geological history and habitat fragmentation. Hence, it can be assumed that particularly high species richness can be found in organisms with limited dispersal capabilities that inhabit mountain streams. A number of scientific papers focus on molecular phylogeography or traditional taxonomy of species or species groups inhabiting such habitats. However, there is a lack of studies that integrate morphological and molecular data to identify and delineate cryptic species. For practical reasons, uncovering cryptic diversity is crucial in taxa used in biomonitoring. Distinct species, hard to separate based on morphology only, may have different tolerance ranges towards a variety of factors. Thus, our goal is to combine the two approaches to reveal potential patterns of diversification within a species widely distributed across European mountains: the amphipod crustacean Gammarus balcanicus. The data were obtained from 13 populations spread across the range of the species. Individuals were initially ascribed to G. balcanicus based on conventional fauna key morpho‐anatomical diagnostic features and were further analysed for 23 additional features to explore any putative diversification. Morphometric data were analysed with use of the multiple correspondence analysis and anova . Molecular distances were calculated for 551‐bp‐long COI sequences. Test for isolation by distance was performed for both morphological and molecular data. The morphometric studies showed that some of the analysed features differed significantly between populations, although there was only a weak correlation between the morphological divergence and the between‐population geographical distances. Moreover, high morphological diversity was present within sites. A set of 42 COI haplotypes was identified among the 135 individuals sequenced. No haplotype was shared among populations. The molecular p‐distances within the nine localities presenting more than one haplotype were either almost null (ca. <0.003 for 7 localities) or relatively low (ca. 0.01–0.02 for 2 localities). In opposite, the molecular p‐distances between localities were mostly at a high level (94% of pairwise comparisons being >0.14), similar as between other well‐defined species of the genus Gammarus. Surprisingly, G. balcanicus appears to be polyphyletic based on topology of the neighbour‐joining tree. The level of genetic distance between localities was not correlated with their geographical proximity. Globally, combining spatial patterns of morphological versus molecular divergence indicates a high level of cryptic diversity within a species conventionally defined based upon fauna key morphological features. In this context, the name G. balcanicus should be applied only to the population from locus typicus, while the other populations represent a number of putative distinct species. We may expect that such phenomenon would apply also to other animal taxa with conserved morphology, which are widespread over different mountain ranges in Europe. 相似文献
86.
87.
Vania Vilas-Boas Renata Silva Andreia Palmeira Emília Sousa Luísa Maria Ferreira Paula Sério Branco Félix Carvalho Maria de Lourdes Bastos Fernando Remi?o 《PloS one》2013,8(8)
P-glycoprotein (P-gp) is a 170 kDa transmembrane protein involved in the outward transport of many structurally unrelated substrates. P-gp activation/induction may function as an antidotal pathway to prevent the cytotoxicity of these substrates. In the present study we aimed at testing rifampicin (Rif) and three newly synthesized Rif derivatives (a mono-methoxylated derivative, MeORif, a peracetylated derivative, PerAcRif, and a reduced derivative, RedRif) to establish their ability to modulate P-gp expression and activity in a cellular model of the rat’s blood–brain barrier, the RBE4 cell line P-gp expression was assessed by western blot using C219 anti-P-gp antibody. P-gp function was evaluated by flow cytometry measuring the accumulation of rhodamine123. Whenever P-gp activation/induction ability was detected in a tested compound, its antidotal effect was further tested using paraquat as cytotoxicity model. Interactions between Rif or its derivatives and P-gp were also investigated by computational analysis. Rif led to a significant increase in P-gp expression at 72 h and RedRif significantly increased both P-gp expression and activity. No significant differences were observed for the other derivatives. Pre- or simultaneous treatment with RedRif protected cells against paraquat-induced cytotoxicity, an effect reverted by GF120918, a P-gp inhibitor, corroborating the observed P-gp activation ability. Interaction of RedRif with P-gp drug-binding pocket was consistent with an activation mechanism of action, which was confirmed with docking studies. Therefore, RedRif protection against paraquat-induced cytotoxicity in RBE4 cells, through P-gp activation/induction, suggests that it may be useful as an antidote for cytotoxic substrates of P-gp. 相似文献
88.
Anton H. Barman Elisabeth W. de Jong Remi Thierry Peter Westbroek Leendert Bosch Marijke Gruter Johannes P. Kamerling 《Journal of phycology》1987,23(1):118-123
Coccoliths of Emiliania huxleyi (Lohmann) Hay and Mohler, a unicellular calcifying alga, consist of calcite closely associated with an acidic, Ca2+-binding polysaccharide. This polysaccharide is thought to play a regulatory role in coccolith synthesis by interfering with CaCO3 crystallization. Here we show that the polysaccharides from three different strains, A 92, L and 92 D, all inhibit the precipitation of CaCO3 in vitro to the same extent. The monosaccharide compositions of the A 92 and L polysaccharide are similar. The 92 D material, however, deviates from the other two: it contains significantly lower amounts of methylated sugars and ribose, and elevated levels of rhamnose and galactose. It also contains antigenic determinants not detected in the A 92 and L polysaccharides. In contrast to the latter two macromolecules the 92 D polysaccharide migrates as two bands upon polyacrylamide gel electrophoresis, possibly resulting from complexing with small amounts of protein. The coccolith polysaccharide from L cells, cultured at an elevated growth rate, also migrates as two bands. This phenomenon is due to an increase in molecular size distribution. The results suggest that certain properties of the molecule may be subject to variation without interfering with its function. 相似文献
89.
Food availability and growth rate in natural populations of the brown trout (Salmo trutta) in Corsican streams 总被引:3,自引:0,他引:3
The rivers of the island of Corsica, whose catchment areas are on crystalline rock, have low salt contents and their invertebrate fauna is qualitatively and quantitatively poorer than on the European mainland. The growth rate of trout in Corsica was analysed on samples from of six coastal rivers: the Tavignano, the Fium Orbo and the Golo on the west coast, the Prunelli, the Taravo and the Rizzanese on the east coast. Mesological data — conductivity, temperature, calcium content and altitude and biological data — biomass and linear growth rate of the trout, and density of benthic invertebrates — were collected at each of the sampling station.Analysis of variance of the size of three year old trout revealed three groups of rivers. The first includes the Tavignano, the Rizzanese and the Taravo, where the highest linear growth rates were recorded; the second consists of the Golo and the Prunelli, and the third, of the Fium Orbo. Principal component analysis gave two main axes on the basis of temperature and benthic invertebrate density for the first, and trout biomass for the second. Linear regression showed that benthic invertebrate density accounted for 75% of size variance of three year old trout. Evidence of the limiting role of the trophic factor is provided. 相似文献
90.
[3H]Pentagastrin binds specifically to an apparent single class of CCK receptors on slide-mounted sections of rat brain (KD=5.6 nM; Bmax=36.6 fmol/mg protein). This specific binding is temperature-dependant and regulated by ions and nucleotides. The relative potencies of C-terminal fragments of CCK-8(SO3H), benzotript and proglumide in inhibiting specific [3H]pentagastrin binding to CCK brain receptors reinforce the concept of different brain and pancreas CCK receptors. CCK receptors were visualized by using tritium-sensitive LKB film analyzed by computerized densitometry. CCK receptors are highly concentrated in the cortex, dentate gyrus, granular and external plexiform layers of the olfactory bulb, anterior olfactory nuclei, olfactory tubercle, claustrum, accumbens nucleus, some nuclei of the amygdala, thalamus and hypothalamus. 相似文献