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131.
Lskow Florian Galbraith Moira D. Hunt Brian P. V. Perry R. Ian Boersma Maarten Pakhomov Evgeny A. 《Hydrobiologia》2022,849(7):1543-1557
Hydrobiologia - Marine ecosystems on continental shelves face multiple challenges due to anthropogenic disturbances, many of which can change the seawater stoichiometry (C:N:P) and consequently... 相似文献
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Decru Eva Vranken Nathan Maetens Heleen Mertens De Vry Amber Kayenbergh Annelies Snoeks Jos Van Steenberge Maarten 《Hydrobiologia》2022,849(8):1743-1762
Hydrobiologia - We present an extensive DNA barcoding study of the fish species of the Lake Edward system, including information on intraspecific variation. The DNA barcode gene, cytochrome c... 相似文献
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Scott Zona Maarten J. M. Christenhusz FLS 《Botanical journal of the Linnean Society. Linnean Society of London》2015,179(4):554-586
Litter‐trapping plants have specialized growth habits and morphologies that enable them to capture falling leaf litter and other debris, which the plants use for nutrition after the litter has decayed. Litter is trapped via rosettes of leaves, specially modified leaves and/or upward‐growing roots (so‐called ‘root baskets’). Litter‐trappers, both epiphytic and terrestrial, are found throughout the tropics, with only a few extra‐tropical species, and they have evolved in many plant families. The trapped litter mass is a source of nutrients for litter‐trapping plants, as well as food and housing for commensal organisms. Despite their unique mode of life, litter‐trapping plants are not well documented, and many questions remain about their distribution, physiology and evolution.–© 2015 The Linnean Society of London, Botanical Journal of the Linnean Society, 2015, 179 , 554–586. 相似文献
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Annemarie Kralt Noorjahan B. Jagalur Vincent van den Boom Ravi K. Lokareddy Anton Steen Gino Cingolani Maarten Fornerod Liesbeth M. Veenhoff 《Molecular biology of the cell》2015,26(18):3301-3312
Endoplasmic reticulum–synthesized membrane proteins traffic through the nuclear pore complex (NPC) en route to the inner nuclear membrane (INM). Although many membrane proteins pass the NPC by simple diffusion, two yeast proteins, ScSrc1/ScHeh1 and ScHeh2, are actively imported. In these proteins, a nuclear localization signal (NLS) and an intrinsically disordered linker encode the sorting signal for recruiting the transport factors for FG-Nup and RanGTP-dependent transport through the NPC. Here we address whether a similar import mechanism applies in metazoans. We show that the (putative) NLSs of metazoan HsSun2, MmLem2, HsLBR, and HsLap2β are not sufficient to drive nuclear accumulation of a membrane protein in yeast, but the NLS from RnPom121 is. This NLS of Pom121 adapts a similar fold as the NLS of Heh2 when transport factor bound and rescues the subcellular localization and synthetic sickness of Heh2ΔNLS mutants. Consistent with the conservation of these NLSs, the NLS and linker of Heh2 support INM localization in HEK293T cells. The conserved features of the NLSs of ScHeh1, ScHeh2, and RnPom121 and the effective sorting of Heh2-derived reporters in human cells suggest that active import is conserved but confined to a small subset of INM proteins. 相似文献
139.
Maarten Van Roy Cedric Ververken Els Beirnaert Sven Hoefman Joost Kolkman Michel Vierboom Elia Breedveld Bert ‘t Hart Sofie Poelmans Lieselot Bontinck Alex Hemeryck Sandy Jacobs Judith Baumeister Hans Ulrichts 《Arthritis research & therapy》2015,17(1)
IntroductionThe pleiotropic cytokine interleukin-6 (IL-6) plays an important role in the pathogenesis of different diseases, including rheumatoid arthritis (RA). ALX-0061 is a bispecific Nanobody® with a high affinity and potency for IL-6 receptor (IL-6R), combined with an extended half-life by targeting human serum albumin. We describe here the relevant aspects of its in vitro and in vivo pharmacology.MethodsALX-0061 is composed of an affinity-matured IL-6R-targeting domain fused to an albumin-binding domain representing a minimized two-domain structure. A panel of different in vitro assays was used to characterize the biological activities of ALX-0061. The pharmacological properties of ALX-0061 were examined in cynomolgus monkeys, using plasma levels of total soluble (s)IL-6R as pharmacodynamic marker. Therapeutic effect was evaluated in a human IL-6-induced acute phase response model in the same species, and in a collagen-induced arthritis (CIA) model in rhesus monkeys, using tocilizumab as positive control.ResultsALX-0061 was designed to confer the desired pharmacological properties. A 200-fold increase of target affinity was obtained through affinity maturation of the parental domain. The high affinity for sIL-6R (0.19 pM) translated to a concentration-dependent and complete neutralization of sIL-6R in vitro. In cynomolgus monkeys, ALX-0061 showed a dose-dependent and complete inhibition of hIL-6-induced inflammatory parameters, including plasma levels of C-reactive protein (CRP), fibrinogen and platelets. An apparent plasma half-life of 6.6 days was observed after a single intravenous administration of 10 mg/kg ALX-0061 in cynomolgus monkeys, similar to the estimated expected half-life of serum albumin. ALX-0061 and tocilizumab demonstrated a marked decrease in serum CRP levels in a non-human primate CIA model. Clinical effect was confirmed in animals with active drug exposure throughout the study duration.ConclusionsALX-0061 represents a minimized bispecific biotherapeutic of 26 kDa, nearly six times smaller than monoclonal antibodies. High in vitro affinity and potency was demonstrated. Albumin binding as a half-life extension technology resulted in describable and expected pharmacokinetics. Strong IL-6R engagement was shown to translate to in vivo effect in non-human primates, demonstrated via biomarker deregulation as well as clinical effect. Presented results on preclinical pharmacological properties of ALX-0061 are supportive of clinical development in RA.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0651-0) contains supplementary material, which is available to authorized users. 相似文献140.
Bacterial cell wall hydrolases (BCWHs) display a remarkable structural and functional diversity that offers perspectives for novel food applications, reaching beyond those of the archetype BCWH and established biopreservative hen egg white lysozyme. Insights in BCWHs from bacteriophages to animals have provided concepts for tailoring BCWHs to target specific pathogens or spoilage bacteria, or, conversely, to expand their working range to Gram-negative bacteria. Genetically modified foods expressing BCWHs in situ showed successful, but face regulatory and ethical concerns. An interesting spin-off development is the use of cell wall binding domains of bacteriophage BCWHs for detection and removal of foodborne pathogens. Besides for improving food safety or stability, BCWHs may also find use as functional food ingredients with specific health effects. 相似文献