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81.
N Rochel G Tocchini-Valentini P F Egea K Juntunen J M Garnier P Vihko D Moras 《European journal of biochemistry》2001,268(4):971-979
Vitamin D nuclear receptor mediates the genomic actions of the active form of vitamin D, 1,25(OH)2D3. This hormone is involved in calcium and phosphate metabolism and cell differentiation. Compared to other nuclear receptors, VDR presents a large insertion region at the N-terminal part of the ligand binding domain between helices H1 and H3, encoded by an additional exon. This region is poorly conserved in VDR in different species and is not well ordered as observed by secondary structure prediction. We engineered a VDR ligand binding domain mutant by removing this insertion region. Here we report its biochemical and biophysical characterization. The mutant protein exhibits the same ligand binding, dimerization with retinoid X receptor and transactivation properties as the wild-type VDR, suggesting that the insertion region does not affect these main functions. Solution studies by small angle X-ray scattering shows that the conformation in solution of the VDR mutant is similar to that observed in the crystal and that the insertion region in the VDR wild-type is not well ordered. 相似文献
82.
Esther Munalula‐Nkandu Paul Ndebele Seter Siziya JC Munthali 《Developing world bioethics》2015,15(3):248-256
We conducted a study to review the consenting process in a vaginal Microbicide feasibility study conducted in Mazabuka, Zambia. Participants were drawn from those participating in the microbicide study. A questionnaire and focus group discussion were used to collect information on participants understanding of study aims, risks and benefits. Altogether, 200 participants took part in this study. The results of the study showed that while all participants signed or endorsed their thumbprints to the consent forms, full informed consent was not attained from most of the participants since 77% (n = 154) of the participants had numerous questions about the study and 34% (n = 68) did not know who to get in touch with concerning the study. Study objectives were not fully understood by over 61% of the participants. Sixty four percent of the participants were not sure of the risks of taking part in the microbicide study. A significant number thought the study was all about determining their HIV status. Some participants were concerned that their partners were not on the trial as they were convinced that being on the study meant that that they had a lifetime protection from HIV infection. The process of obtaining consent was inadequate as various phases of the study were not fully understood. We recommend the need for researchers to reinforce the consenting process in all studies and more so when studies are conducted in low literacy populations. 相似文献
83.
In spite of the increasing application of DNA fingerprinting to natural
populations and to the genetic identification of humans, explicit methods
for estimation of basic population genetic parameters from DNA
fingerprinting data have not been developed. Contributing to this omission
is the inability to determine, for multilocus fingerprinting probes,
relatively important genetic information, such as the number of loci, the
number of alleles, and the distribution of these alleles into specific
loci. One of the most useful genetic parameters that could be derived from
such data would be the average heterozygosity, which has traditionally been
employed to measure the level of genetic variation within populations and
to compare genetic variation among different loci. We derive here explicit
formulas for both the estimation of average heterozygosity at multiple
hypervariable loci and a maximum value for this estimate. These estimates
are based upon the DNA restriction-pattern matrices that are typical for
fingerprinting studies of humans and natural populations. For several
empirical data sets from our laboratory, estimates of average and maximal
heterozygosity are shown to be relatively close to each other. Furthermore,
variances of these statistics based on simulation studies are relatively
small. These observations, as well as consideration of the effect of
missing alleles and alternate numbers of loci, suggest that the average
heterozygosity can be accurately estimated using phenotypic DNA fingerprint
patterns, because this parameter is relatively insensitive to the lack of
certain genetic information.
相似文献
84.
85.
Martínez-Alonso E Egea G Ballesta J Martínez-Menárguez JA 《Traffic (Copenhagen, Denmark)》2005,6(1):32-44
Immunofluorescence and cryoimmunoelectron microscopy were used to examine the morphologic and functional effects on the Golgi complex when protein transport is blocked at the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) in HeLa cells incubated at low temperature (15 degrees C). At this temperature, the Golgi complex showed long tubules containing resident glycosylation enzymes but not matrix proteins. These Golgi-derived tubules also lacked anterograde (VSV-G) or retrograde (Shiga toxin) cargo. The formation of tubules was dependent on both energy and intact microtubule and actin cytoskeletons. Conversely, brefeldin A or cycloheximide treatments did not modify the appearance. When examined at the electron microscope, Golgi stacks were long and curved and appeared connected to tubules immunoreactive to galactosyltransferase antibodies but devoid of Golgi matrix proteins. Strikingly, COPI proteins moved from membranes to the cytosol at 15 degrees C, which could explain the formation of tubules. 相似文献
86.
Tomás M Fornas E Megías L Durán JM Portolés M Guerri C Egea G Renau-Piqueras J 《Journal of neurochemistry》2002,83(3):601-612
Astrocyte and glial-neuron interactions have a critical role in brain development, which is partially mediated by glycoproteins, including adhesion molecules and growth factors. Ethanol affects the synthesis, intracellular transport, subcellular distribution and secretion of these glycoproteins, suggesting alterations in glycosylation. We analyzed the effect of long-term exposure to low doses of ethanol (30 mm) on glycosylation process in growing cultured astrocytes in vitro. Cells were incubated for short (5 min) and long (90 min) periods with several radioactively labeled carbohydrate precursors. The uptake, kinetics and metabolism of these precursors, as well as the radioactivity distribution in protein gels were analyzed. The levels of GLUT1 and mannosidase II were also determined. Ethanol increased the uptake of monosaccharides and the protein levels of GLUT1 but decreased those of mannosidase II. It altered the carbohydrate moiety of proteins and increased cell surface glycoproteins containing terminal non-reduced mannose. These results indicate that ethanol impairs glycosylation in rat astrocytes, thus disrupting brain development. 相似文献
87.
Endocytosis of NBD-sphingolipids in neurons: exclusion from degradative compartments and transport to the Golgi complex 总被引:1,自引:1,他引:0
Babià T Ledesma MD Saffrich R Kok JW Dotti CG Egea G 《Traffic (Copenhagen, Denmark)》2001,2(6):395-405
Sphingolipids are abundant constituents of neuronal membranes that have been implicated in intracellular signaling, neurite outgrowth and differentiation. Differential localization and trafficking of lipids to membrane domains contribute to the specialized functions. In non-neuronal cultured cell lines, plasma membrane short-chain sphingomyelin and glucosylceramide are recycled via endosomes or sorted to degradative compartments. However, depending on cell type and lipid membrane composition, short-chain glucosylceramide can also be diverted to the Golgi complex. Here, we show that NBD-labeled glucosylceramide and sphingomyelin are transported from the plasma membrane to the Golgi complex in cultured rat hippocampal neurons irrespective of the stage of neuronal differentiation. Golgi complex localization was confirmed by colocalization and Golgi disruption studies, and importantly did not result from conversion of NBD-glucosylceramide or NBD-sphingomyelin to NBD-ceramide. Double-labeling experiments with transferrin or wheat-germ agglutinin showed that NBD-sphingolipids are first internalized to early/recycling endosomes, and subsequently transported to the Golgi complex. The internalization of these two sphingolipid analogs was energy and temperature dependent, and their intracellular transport was insensitive to the NBD fluorescence quencher sodium dithionite. These results indicate that vesicles mediate the transport of internalized NBD-glucosylceramide and NBD-sphingomyelin to the Golgi complex. 相似文献
88.
Jos�� M. Mir��s-Avalos Gregorio Egea Emilio Nicol��s Michel G��nard Gilles Vercambre Nicolas Moitrier Pierre Valsesia Mar��a M. Gonz��lez-Real Claude Bussi Fran?oise Lescourret 《Trees - Structure and Function》2011,25(5):785-799
In this paper, QualiTree, a fruit tree model designed to study the management of fruit quality, and developed and described
in a companion paper (Lescourret et al. in Trees Struct Funct, 2010), was combined with a simple light-interception sub-model, and then parameterised and tested on peach in different situations.
Simulation outputs displayed fairly good agreement with the observed data concerning mean fruit and vegetative growth. The
variability over time of fruit and vegetative growth was well predicted. QualiTree was able to reproduce the observed response
of trees to heterogeneous thinning treatments in terms of fruit growth. A sensitivity analysis showed that the average seasonal
growth rates of the different organs were sensitive to changes to the values of their respective initial relative growth rates
and that stem wood was the tree organ the most affected by a change in the initial relative growth rates of other organs.
QualiTree was able to react to simulated scenarios that combined thinning and pest attacks. As expected, thinning intensity
and the percentage damage caused by pests significantly affected fruit yield and quality traits at harvest. These simulations
showed that QualiTree could be a useful tool to design innovative horticultural practices. 相似文献
89.
90.
Paul REL Lafond T Müller-Graf CDM Nithiuthai S Brey PT Koella JC 《BMC evolutionary biology》2004,4(1):1-13