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991.
Since protein patterning on 2D surfaces has emerged as an important tool in cell biology, the development of easy patterning methods has gained importance in biology labs. In this paper we present a simple, rapid and reliable technique to fabricate thin layers of UV curable polymer with through holes. These membranes are as easy to fabricate as microcontact printing stamps and can be readily used for stencil patterning. We show how this microfabrication scheme allows highly reproducible and highly homogeneous protein patterning with micron sized resolution on surfaces as large as 10 cm(2). Using these stencils, fragile proteins were patterned without loss of function in a fully hydrated state. We further demonstrate how intricate patterns of multiple proteins can be achieved by stacking the stencil membranes. We termed this approach microserigraphy. 相似文献
992.
Maury Y Gauthier M Peschanski M Martinat C 《BioEssays : news and reviews in molecular, cellular and developmental biology》2012,34(1):61-71
Considerable hope surrounds the use of disease-specific pluripotent stem cells to generate models of human disease allowing exploration of pathological mechanisms and search for new treatments. Disease-specific human embryonic stem cells were the first to provide a useful source for studying certain disease states. The recent demonstration that human somatic cells, derived from readily accessible tissue such as skin or blood, can be converted to embryonic-like induced pluripotent stem cells (hiPSCs) has opened new perspectives for modelling and understanding a larger number of human pathologies. In this review, we examine the opportunities and challenges for the use of disease-specific pluripotent stem cells in disease modelling and drug screening. Progress in these areas will substantially accelerate effective application of disease-specific human pluripotent stem cells for drug screening. 相似文献
993.
994.
Bukhari IA Shah AJ Gauthier KM Walsh KA Koduru SR Imig JD Falck JR Campbell WB 《American journal of physiology. Heart and circulatory physiology》2012,302(8):H1574-H1583
Arachidonic acid is metabolized to four regioisomeric epoxyeicosatrienoic acids (EETs) by cytochrome P-450. 5,6-, 8,9-, 11,12-, and 14,15-EET are equipotent in relaxing bovine coronary arteries (BCAs). Vasorelaxant effects of EETs are nonselectively antagonized by 14,15-epoxyeicosa-5(Z)-enoic acid. The 11,12-EET analogs, 20-hydroxy-11,12-epoxyeicosa-8(Z)-enoic acid (20-H-11,12-EE8ZE) and 11,12,20-trihydroxyeicosa-8(Z)-enoic acid (11,12,20-THE8ZE) were synthesized and tested for antagonist activity against EET-induced relaxations in BCAs. In U-46619-preconstricted arterial rings, 5,6-, 8,9-, 11,12-, and 14,15-EET caused concentration-dependent relaxations with maximal relaxations ranging from 80 to 96%. Preincubation of arteries with 20-H-11,12-EE8ZE (10(-5) M) inhibited relaxations to 14,15- and 11,12-EET, but not 5,6- and 8,9-EET; however, greatest inhibitory effect was against 11,12-EET (maximal relaxation = 80.6 ± 4.6 vs. 26.7 ± 7.4% without and with 20-H-11,12-EE8ZE, respectively). Preincubation with the soluble epoxide hydrolase inhibitor (tAUCB, 10(-6) M) significantly enhanced the antagonist effect of 20-H-11,12-EE8ZE against 14,15-EET-induced relaxations (maximal relaxation = 86.6 ± 4.4 vs. 27.8 ± 3.3%, without and with 20-H-11,12-EE8ZE and tAUCB) without any change in its effect against 11,12-EET-induced relaxations. In contrast to the parent compound, the metabolite, 11,12,20-THE8ZE (10(-5) M), significantly inhibited relaxations to 11,12-EET and was without effect on other EET regioisomers. Mass spectrometric analysis revealed conversion of 20-H-11,12-EE8ZE to 11,12,20-THE8ZE by incubation with BCA. The conversion was blocked by tAUCB. 14,15-Dihydroxy-eicosa-5Z-enoic acid (a 14,15-EET antagonist), but not 11,12,20-THE8ZE (an 11,12-EET antagonist), inhibited BCA relaxations to arachidonic acid and flow-induced dilation in rat mesenteric arteries. These results indicate that 11,12,20-THE8ZE is a selective antagonist of 11,12-EET relaxations and a useful pharmacological tool to elucidate the function of 11,12-EET in the cardiovascular system. 相似文献
995.
Latifa Elantak Marion Espeli Annie Boned Olivier Bornet Jeremy Bonzi Laurent Gauthier Mikael Feracci Philippe Roche Fran?oise Guerlesquin Claudine Schiff 《The Journal of biological chemistry》2012,287(53):44703-44713
During B cell differentiation in the bone marrow, the expression and activation of the pre-B cell receptor (pre-BCR) constitute crucial checkpoints for B cell development. Both constitutive and ligand-dependent pre-BCR activation modes have been described. The pre-BCR constitutes an immunoglobulin heavy chain (Igμ) and a surrogate light chain composed of the invariant λ5 and VpreB proteins. We previously showed that galectin-1 (GAL1), produced by bone marrow stromal cells, is a pre-BCR ligand that induces receptor clustering, leading to efficient pre-BII cell proliferation and differentiation. GAL1 interacts with the pre-BCR via the unique region of λ5 (λ5-UR). Here, we investigated the solution structure of a minimal λ5-UR motif that interacts with GAL1. This motif adopts a stable helical conformation that docks onto a GAL1 hydrophobic surface adjacent to its carbohydrate binding site. We identified key hydrophobic residues from the λ5-UR as crucial for the interaction with GAL1 and for pre-BCR clustering. These residues involved in GAL1-induced pre-BCR activation are different from those essential for autonomous receptor activation. Overall, our results indicate that constitutive and ligand-induced pre-BCR activation could occur in a complementary manner. 相似文献
996.
Reid DG Bilodeau F Krebs CJ Gauthier G Kenney AJ Gilbert BS Leung MC Duchesne D Hofer E 《Oecologia》2012,168(4):935-946
The insulative value of early and deep winter snow is thought to enhance winter reproduction and survival by arctic lemmings
(Lemmus and Dicrostonyx spp). This leads to the general hypothesis that landscapes with persistently low lemming population densities, or low amplitude
population fluctuations, have a low proportion of the land base with deep snow. We experimentally tested a component of this
hypothesis, that snow depth influences habitat choice, at three Canadian Arctic sites: Bylot Island, Nunavut; Herschel Island,
Yukon; Komakuk Beach, Yukon. We used snow fencing to enhance snow depth on 9-ha tundra habitats, and measured the intensity
of winter use of these and control areas by counting rodent winter nests in spring. At all three sites, the density of winter
nests increased in treated areas compared to control areas after the treatment, and remained higher on treated areas during
the treatment. The treatment was relaxed at one site, and winter nest density returned to pre-treatment levels. The rodents’
proportional use of treated areas compared to adjacent control areas increased and remained higher during the treatment. At
two of three sites, lemmings and voles showed significant attraction to the areas of deepest snow accumulation closest to
the fences. The strength of the treatment effect appeared to depend on how quickly the ground level temperature regime became
stable in autumn, coincident with snow depths near the hiemal threshold. Our results provide strong support for the hypothesis
that snow depth is a primary determinant of winter habitat choice by tundra lemmings and voles. 相似文献
997.
Zhang Z Kodumuru V Sviridov S Liu S Chafeev M Chowdhury S Chakka N Sun J Gauthier SJ Mattice M Ratkay LG Kwan R Thompson J Cutts AB Fu J Kamboj R Goldberg YP Cadieux JA 《Bioorganic & medicinal chemistry letters》2012,22(15):5108-5113
Inhibition of intestinal brush border DMT1 offers a novel therapeutic approach to the prevention and treatment of disorders of iron overload. Several series of diaryl and tricyclic benzylisothiourea compounds as novel and potent DMT1 inhibitors were discovered from the original hit compound 1. These compounds demonstrated in vitro potency against DMT1, desirable cell permeability properties and a dose-dependent inhibition of iron uptake in an acute rat model of iron hyperabsorption. Tricyclic compounds increased the in vitro potency by up to 16-fold versus the original hit. Diaryl compounds 6b and 14a demonstrated significant iron absorption inhibition in vivo with both 25 and 50 mg/kg doses. The diaryl and tricyclic compounds described in this report represent promising structural templates for further optimization. 相似文献
998.
Legagneux P Fast PL Gauthier G Bêty J 《Proceedings. Biological sciences / The Royal Society》2012,279(1730):876-883
Despite observational evidence of carry-over effects (COEs, events occurring in one season that produce residual effects on individuals the following seasons), to our knowledge no experimental studies have been carried out to explore how COEs might affect reproductive output. We simulated an environmental perturbation affecting spring-staging migrants to investigate COEs in greater snow geese (Anser caerulescens atlanticus). During three consecutive years, 2037 females captured during spring staging (approx. 3000 km south of their Arctic breeding grounds) were maintained in captivity (with or without access to food) for 0-4 days. Duration of captivity (but not food treatment) negatively affected reproductive success, probably through stress response. Reproductive success was reduced by 45-71% in 2 years, but not in a third year with unusually favourable breeding conditions. This unprecedented manipulation indicates that COEs can have a strong effect on individual reproductive success in long-distance migrants, but that this effect can be partly compensated for by good environmental conditions on the breeding ground. 相似文献
999.
1000.
Thompson John D. Amiot Justin Borron Christophe Linhart Yan B. Keeefover-Ring Ken Gauthier Perrine 《Plant Ecology》2019,220(7-8):777-788
Plant Ecology - The utilization of host plants by herbivorous insects depends on plant traits and physical environment. The purpose of the present work is to test the hypothesis that spatial... 相似文献