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排序方式: 共有653条查询结果,搜索用时 15 毫秒
61.
Bainbridge J Madden L Essex D Binks M Malhotra R Paleolog EM 《Arthritis research & therapy》2007,9(6):R127
The enzyme methionine aminopeptidase-2 (MetAP-2) is thought to play an important function in human endothelial cell proliferation,
and as such provides a valuable target in both inflammation and cancer. Rheumatoid arthritis (RA) is a chronic inflammatory
disease associated with increased synovial vascularity, and hence is a potential therapeutic target for angiogenesis inhibitors.
We examined the use of PPI-2458, a selective non-reversible inhibitor of MetAP-2, in disease models of RA, namely acute and
chronic collagen-induced arthritis (CIA) in mice. Whilst acute CIA is a monophasic disease, CIA induced with murine collagen
type II manifests as a chronic relapsing arthritis and mimics more closely the disease course of RA. Our study showed PPI-2458
was able to reduce clinical signs of arthritis in both acute and chronic CIA models. This reduction in arthritis was paralleled
by decreased joint inflammation and destruction. Detailed mechanism of action studies demonstrated that PPI-2458 inhibited
human endothelial cell proliferation and angiogenesis in vitro, without affecting production of inflammatory cytokines. Furthermore, we also investigated release of inflammatory cytokines
and chemokines from human RA synovial cell cultures, and observed no effect of PPI-2458 on spontaneous expression of cytokines
and chemokines, or indeed on the angiogenic molecule vascular endothelial growth factor (VEGF). These results highlight MetAP-2
as a good candidate for therapeutic intervention in RA. 相似文献
62.
Chua Jia Wang Madden Leigh Lim Sophia Beng Hui Philips Anthony R. J. Becker David L. 《Molecular and cellular biochemistry》2022,477(1):295-305
Molecular and Cellular Biochemistry - Despite many advances across the surgical sciences, post-surgical peritoneal adhesions still pose a considerable risk in modern-day procedures and are highly... 相似文献
63.
64.
Male brood provisioning rates provide evidence for inter‐age competition for mates in female Cooper's Hawks Accipiter cooperii
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Life history theory predicts that individuals should maximize lifetime reproductive success (LRS) by breeding as soon as they reach sexual maturity, yet many species delay breeding, either because there are insufficient available mates or breeding sites, or because delayed breeding yields higher LRS. Accipitriform species, such as Cooper's Hawk Accipiter cooperii, exhibit both delayed breeding and delayed plumage maturation. However, in certain circumstances, first‐year females in non‐definitive plumage do breed and apparently compete with older females for high‐quality breeding territories. We predicted that these young females are at a competitive disadvantage compared with older females and that older females would have both higher reproductive success and be able to acquire higher quality nesting territories. We conducted brood counts and measured prey delivery rates by male Cooper's Hawks in an expanding urban population located in Albuquerque, New Mexico (USA), to assess our prediction. We found that older females had higher reproductive success, fledging 1.6 more offspring than younger females, and that they occupied territories where males provisioned at higher rates of 0.37 more prey items per 2‐h period. Our results showed that older females fared better than first‐year females but it is unclear if this is the result of passive or active competition. Older females initiated nesting 14.3 days sooner than first‐year females and thus may have filled vacant, high‐quality territories before first‐year females began seeking mates. Additionally, first‐year females were never observed persistently to confront older females for breeding territories, but they did actively compete against each other. First‐year females may defer to older females who, in a direct competitive interaction, would be most likely to prevail. Thus, delayed plumage maturation in Cooper's Hawks may serve to focus competition for nesting territories within age classes. 相似文献
65.
Lee Taylor Adrian W. Midgley Bryna Chrismas Angela R. Hilman Leigh A. Madden Rebecca V. Vince Lars R. McNaughton 《Amino acids》2011,40(2):393-401
Heat shock protein 72 (HSP72) performs vital roles within the body at rest and during periods of stress. In vitro, research
demonstrates HSP72 induction in response to hypoxia. Recently, in vivo, an acute hypoxic exposure (75 min at 2,980 m) was
sufficient to induce significant increases in monocyte expressed HSP72 (mHSP72) and a marker of oxidative stress in healthy human subjects. The purpose of the current study was to identify the impact
of 10 consecutive days of hypoxic exposures (75 min at 2,980 m) on mHSP72 and erythropoietin (EPO) expression, markers of oxidative stress, and maximal oxygen consumption in graded incremental aerobic
exercise. Eight male subjects were exposed to daily normobaric hypoxic exposures for 75 min at 2,980 m for 10 consecutive
days, commencing and ceasing at 0930 and 1045, respectively. This stressor was sufficient to induce significant increases
in mHSP72, which was significantly elevated from day 2 of the hypoxic exposures until 48 h post-final exposure. Notably, this increase
had an initial rapid (30% day on day compared to baseline) and final slow phase (16% day on day compared to baseline) of expression.
The authors postulate that 7-day hypoxic exposure in this manner would be sufficient to induce near maximum hypoxia-mediated
basal mHSP72 expression. Elevated levels of mHSP72 are associated with acquired thermotolerance and provide cross tolerance to non-related stressors in vivo, the protocol used
here may provide a useful tool for elevating mHSP72 in vivo. Aside from these major findings, significant transient daily elevations were seen in a marker of oxidative stress,
alongside sustained increases in EPO expression. However, no physiologically significant changes were seen in maximal oxygen
consumption or time to exhaustion. 相似文献
66.
Madden JR Clutton-Brock TH 《Proceedings. Biological sciences / The Royal Society》2011,278(1709):1189-1194
The evolution and expression of different forms of cooperative behaviour (e.g. feeding, guarding, sentinel duties, etc.) are usually studied independently, with few studies considering them as a single syndrome. However, studies investigating individuals' investment across a suite of different behaviours reveal that they are correlated, suggesting a single mechanism determining the evolution and expression of cooperative behaviours. A hormonal mechanism could achieve this, and one possibility is oxytocin (OT), which affects several prosocial or alloparental behaviours independently. We show, using a double-blind experiment, that peripheral administration of OT to social, free-living meerkats Suricata suricatta elevates a suite of cooperative behaviours. Treated individuals increase their contributions to communal, cooperative activities (digging, guarding, pup-feeding and associating with pups) and decrease initiation of aggressive interactions, compared with a saline control. This suggests that different forms of cooperative behaviour form a single syndrome with a common causal basis. If our peripherally administered OT acts in the same way as the naturally released hormone, then a general tendency to prosociality may be modulated by this hormonal system. Therefore, it may be difficult for an individual to decouple expression of cooperative behaviours that provide the practitioner with benefits from those that provide the recipient with benefits. It may also explain why social species typically exhibit a suite of cooperative behaviours, without having to invoke independent evolution of each. 相似文献
67.
Gompels LL Malik NM Madden L Jin P Feldmann M Shepard HM Paleolog EM 《Arthritis research & therapy》2011,13(5):R161
Introduction
Rheumatoid arthritis (RA) is a chronic disease associated with inflammation and destruction of bone and cartilage. Although inhibition of TNFα is widely used to treat RA, a significant number of patients do not respond to TNFα blockade, and therefore there is a compelling need to continue to identify alternative therapeutic strategies for treating chronic inflammatory diseases such as RA. The anti-epidermal growth factor (anti-EGF) receptor antibody trastuzumab has revolutionised the treatment of patients with EGF receptor-positive breast cancer. Expression of EGF ligands and receptors (known as HER) has also been documented in RA. The highly unique compound RB200 is a bispecific ligand trap that is composed of full-length extracellular domains of HER1 and HER3 EGF receptors. Because of its pan-HER specificity, RB200 inhibits responses mediated by HER1, HER2 and HER3 in vitro and in vivo. The objective of this study was to assess the effect of RB200 combined with TNF blockade in a murine collagen-induced arthritis (CIA) model of RA. 相似文献68.
Gordon D Madden B Krishnan J Klassen S Dalmasso J Theriault S 《Journal of applied microbiology》2011,110(2):455-462
Aims: This study was undertaken to determine the effectiveness of biological indicators currently being employed during formaldehyde decontamination. Data suggest that detectable amounts of formaldehyde are absorbed into the paper strips contained in currently used biological indicators. Absorbed formaldehyde has the potential to inhibit the growth of indicator spores, thus leading to false negative results. Indicators composed of either stainless steel carriers or paper strips were investigated to determine whether stainless steel carriers can be used as an alternative to paper strip indicators. Methods and Results: Biological indicators were exposed to formaldehyde gas and were tested for the presence of formaldehyde and any possible inhibition of spore growth. Absorbed formaldehyde was detected in the paper strip carriers while no formaldehyde was detected from any of the stainless steel carriers. Exposed paper strips were found to inhibit growth of up to 1 × 106 spores while the stainless steel carriers did not inhibit the growth of spores. Conclusions: During decontamination, biological indicators composed of paper spore strips absorb formaldehyde and inhibit growth of any surviving spores. Stainless steel carriers do not absorb formaldehyde and are an ideal alternative substrate for biological indicators. Significance and Impact of the Study: The popular paper strip biological indicator can lead to false negative results during decontamination and is unsuitable for validating formaldehyde decontamination. 相似文献
69.
Banerjee S Paik R Mino RE Blauth K Fisher ES Madden VJ Fanning AS Bhat MA 《PloS one》2011,6(10):e25926
Septate junctions (SJs) display a unique ultrastructural morphology with ladder-like electron densities that are conserved through evolution. Genetic and molecular analyses have identified a highly conserved core complex of SJ proteins consisting of three cell adhesion molecules Neurexin IV, Contactin, and Neuroglian, which interact with the cytoskeletal FERM domain protein Coracle. How these individual proteins interact to form the septal arrays that create the paracellular barrier is poorly understood. Here, we show that point mutations that map to specific domains of neurexin IV lead to formation of fewer septae and disorganization of SJs. Consistent with these observations, our in vivo domain deletion analyses identified the first Laminin G-EGF-Laminin G module in the extracellular region of Neurexin IV as necessary for the localization of and association with Contactin. Neurexin IV protein that is devoid of its cytoplasmic region is able to create septae, but fails to form a full complement of SJs. These data provide the first in vivo evidence that specific domains in Neurexin IV are required for protein-protein interactions and organization of SJs. Given the molecular conservation of SJ proteins across species, our studies may provide insights into how vertebrate axo-glial SJs are organized in myelinated axons. 相似文献
70.
Jaren?I.?Madden Cynthia?S.?JonesEmail author Carol?A.?Auer 《In vitro cellular & developmental biology. Plant》2005,41(1):37-46
Summary Modes of regeneration from hypocotyl explants were studied in Pelargonium × hortorum ‘Scarlet Orbit,’ and three wild relatives, P. zonale, P. alchemilloides, and P. inquinans, on different cytokinin treatments [1 μM thidiazuron (TDZ), 4 μM TDZ, or 8 μM N6-benzylaminopurine (BA) and 1 μM indole-3-acetic acid (IAA)]. P. × hortorum ‘Scarlet Orbit’ and P. zonale showed similar high numbers of easily detached, embryo-like structures in response to 1 μM TDZ; P. alchemilloides and P. inquinans showed weak embryogenic responses to all treatments. To revisit whether P. × hortorum produces somatic embryos, and to examine modes of regeneration in the wild species, the histology of regenerating structures
on hypocotyl explants in 1 μM TDZ was examined. Both P. × hortorum and P. zonale produced embryo-like structures from single cell derivatives of epidermal cells. Globular-shaped structures transitioned
into heart-shaped structures that had loose attachments to explant surfaces and no vascular connection to the explant. Roots
with direct vascular connections to the rest of the embryo-like structures were never observed; root organogenesis appeared
to be secondary. We propose that P. × hortorum and P. zonale exhibit partial somatic embryogenesis, in which all of the criteria for somatic embryos are met except formation of a root
pole. In both species, explants forming embryo-like structures could also undergo shoot organogenesis, where shoots exhibited
a broad base of attachment to the explant and a vascular connection to vascular nodules within the explant. Epidermally derived
embryo-like structures were not observed in P. alchemilloides or P. inquinans in response to 1 μM TDZ. Shoot organogenesis occurred in P. alchemilloides but not in P. inquinans. 相似文献