全文获取类型
收费全文 | 966篇 |
免费 | 63篇 |
出版年
2023年 | 3篇 |
2022年 | 9篇 |
2021年 | 33篇 |
2020年 | 12篇 |
2019年 | 24篇 |
2018年 | 31篇 |
2017年 | 16篇 |
2016年 | 23篇 |
2015年 | 50篇 |
2014年 | 52篇 |
2013年 | 64篇 |
2012年 | 90篇 |
2011年 | 86篇 |
2010年 | 64篇 |
2009年 | 44篇 |
2008年 | 61篇 |
2007年 | 72篇 |
2006年 | 50篇 |
2005年 | 33篇 |
2004年 | 37篇 |
2003年 | 31篇 |
2002年 | 53篇 |
2001年 | 11篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1998年 | 12篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有1029条查询结果,搜索用时 15 毫秒
81.
82.
Mark Schaller Damian R. Murray Adrian Bangerter 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2015,370(1669)
The ‘behavioural immune system’ is composed of mechanisms that evolved as a means of facilitating behaviours that minimized infection risk and enhanced fitness. Recent empirical research on human populations suggests that these mechanisms have unique consequences for many aspects of human sociality—including sexual attitudes, gregariousness, xenophobia, conformity to majority opinion and conservative sociopolitical attitudes. Throughout much of human evolutionary history, these consequences may have had beneficial health implications; but health implications in modern human societies remain unclear. This article summarizes pertinent ways in which modern human societies are similar to and different from the ecologies within which the behavioural immune system evolved. By attending to these similarities and differences, we identify a set of plausible implications—both positive and negative—that the behavioural immune system may have on health outcomes in contemporary human contexts. We discuss both individual-level infection risk and population-level epidemiological outcomes. We also discuss a variety of additional implications, including compliance with public health policies, the adoption of novel therapeutic interventions and actual immunological functioning. Research on the behavioural immune system, and its implications in contemporary human societies, can provide unique insights into relationships between fitness, sociality and health. 相似文献
83.
Serena C. Hedgepeth M. Iveth Garcia Larry E. Wagner II Ana M. Rodriguez Sree V. Chintapalli Russell R. Snyder Gary D. V. Hankins Beric R. Henderson Kirsty M. Brodie David I. Yule Damian B. van Rossum Darren Boehning 《The Journal of biological chemistry》2015,290(11):7304-7313
The inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitously expressed endoplasmic reticulum (ER)-resident calcium channel. Calcium release mediated by IP3Rs influences many signaling pathways, including those regulating apoptosis. IP3R activity is regulated by protein-protein interactions, including binding to proto-oncogenes and tumor suppressors to regulate cell death. Here we show that the IP3R binds to the tumor suppressor BRCA1. BRCA1 binding directly sensitizes the IP3R to its ligand, IP3. BRCA1 is recruited to the ER during apoptosis in an IP3R-dependent manner, and, in addition, a pool of BRCA1 protein is constitutively associated with the ER under non-apoptotic conditions. This is likely mediated by a novel lipid binding activity of the first BRCA1 C terminus domain of BRCA1. These findings provide a mechanistic explanation by which BRCA1 can act as a proapoptotic protein. 相似文献
84.
p53 Modulates Notch Signaling in MCF‐7 Breast Cancer Cells by Associating With the Notch Transcriptional Complex Via MAML1 下载免费PDF全文
Jieun Yun Ingrid Espinoza Antonio Pannuti Damian Romero Luis Martinez Mary Caskey Adina Stanculescu Maurizio Bocchetta Paola Rizzo Vimla Band Hamid Band Hwan Mook Kim Song‐Kyu Park Keon Wook Kang Maria Laura Avantaggiati Christian R. Gomez Todd Golde Barbara Osborne Lucio Miele 《Journal of cellular physiology》2015,230(12):3115-3127
85.
Ecological niche breadth and microhabitat guild structure in temperate Australian reptiles: Implications for natural resource management in endangered grassy woodland ecosystems 下载免费PDF全文
Damian R. Michael Geoffrey M. Kay Mason Crane Daniel Florance Christopher MacGregor Sachiko Okada Lachlan McBurney David Blair David B. Lindenmayer 《Austral ecology》2015,40(6):651-660
Ecological theory predicts that species with narrow niche requirements (habitat specialists) are more vulnerable to anthropocentric disturbances than those with broad niche requirements (habitat generalists). Hence, understanding a species ecological niche and guild membership would serve as a valuable management tool for providing a priori assessments of a species extinction risk. It also would help to forecast a species capacity to respond to land use change, as what might be expected to occur under financial incentive schemes to improve threatened ecological vegetation communities. However, basic natural history information is lacking for many terrestrial species, particularly reptiles in temperate regions of the world. To overcome this limitation, we collated 3527 reptile observations from 52 species across an endangered woodland ecoregion in south‐eastern Australia and examined ecological niche breadth and microhabitat guild structure. We found 30% of species had low ecological niche values and were classified as habitat specialists associated with large eucalypt trees, woody debris, surface rock or rocky outcrops. Cluster analysis separated species into six broad guilds based on microhabitat similarity. Approximately 80% of species belonged to guilds associated with old growth vegetation attributes or non‐renewable litho‐resources such as surface rock or rocky outcrops. Our results suggest that agri‐environment schemes that focus purely on grazing management are unlikely to provide immediate benefits to broad suites of reptiles associated with old growth vegetation and litho‐resources. Our classification scheme will be useful for identifying reptile species that are potentially vulnerable to anthropocentric disturbances and may require alternative strategies for improving habitat suitability and reptile conservation outcomes in grassy woodland ecosystems. 相似文献
86.
Autotaxin (ATX) is an attractive target for the anticancer therapeutics that inhibits angiogenesis, invasion and migration. ATX is an extracellular lysophospholipase D that hydrolyzes lysophosphatidylcholine to form the bioactive lipid lysophosphatidic acid. The aromatic phosphonate S32826 was the first described nanomolar inhibitor of ATX. However, the tridecylamide substituent on aromatic ring contributed to its poor solubility and bioavailability, severely limiting its utility in vivo. c Log P calculations revealed that the lipophilicity of S32826 could be lowered by shortening its hydrophobic chain and by introducing substituents alpha to the phosphonate. Herein, we describe the synthesis of a small set of α-substituted phosphonate analogs of S32826, and we show that shortening the chain and adding α-halo or α-hydroxy substituents increased solubility; however, ATX inhibition was reduced by most substitutions. An optimal compound was identified for examination of biological effects of ATX inhibition in vivo. 相似文献
87.
Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma. 相似文献
88.
This paper investigates the thermodynamics of gas-phase CO2 cascade uptake-reactions in the form of carbonate or monomethylcarbonate anions in the host cavity of various dinuclear octa-azacryptates
of m-CH2C6H4CH2 and 2,5-furano-spaced hosts, L
1 and L
2 cryptands, using density functional theory (DFT). The cascade process involves two stages, namely the formation of dinuclear
cryptate complexes, and the subsequent formation of either μ-carbonato cryptate complexes or μ-monomethylcarbonato cryptates.
The geometric and electronic structures were also investigated to determine the parameters that affect the stability of the
complexes. Natural bond orbital (NBO) analysis was used to investigate the interactions between the trapped anion and its
host. Ion selectivity was studied in terms of the formation of dinuclear cryptate complexes, while the basicity and nucleophilicity
of cryptands towards Lewis acids was also studied, and good agreement was found vis-à-vis available experimental data. 相似文献
89.
Trans-resveratrol, a natural phytoalexin present in red wine and grapes, has gained considerable attention because of its antiproliferative, chemopreventive and proapoptotic activity against human cancer cells. The accurate quantum-chemical computations based on the density functional theory (DFT) and ab initio second-order Møller-Plesset perturbation method (MP2) have been performed for the first time to study interactions of trans-resveratrol with guanine-thymine dinucleotide and DNA-derived nitrogenous bases: adenine, guanine, cytosine and thymine in vacuum and water medium. This compound is found to show high affinity to nitrogenous bases and guanine-thymine dinucleotide. The electrostatic interactions from intermolecular hydrogen bonding increase the stability of complexes studied. In particular, significantly strong hydrogen bonds between 4′-H atom of trans-resveratrol and imidazole nitrogen as well as carbonyl oxygen atoms of nucleobases studied stabilize these systems. The stabilization energies computed reveal that the negatively charged trans-resveratrol-dinucleotide complex is more energetically stable in water medium than in vacuum. MP2 method gives more reliable and significantly high values of stabilization energy of trans-resveratrol-dinucleotide, trans-resveratrol-guanine and trans-resveratrol-thymine complexes than B3LYP exchange-correlation functional because it takes into account London dispersion energy. According to the results, in the presence of trans-resveratrol the 3′-5′ phosphodiester bond in dinucleotide can be cleaved and the proton from 4′-OH group of trans-resveratrol migrates to the 3′-O atom of dinucleotide. It is concluded that trans-resveratrol is able to break the DNA strand. Hence, the findings obtained help understand antiproliferative and anticancer properties of this polyphenol. 相似文献
90.
A variety of pathologies such as skeletal fracture, neoplasia and inflammation compromise tissue perfusion and thereby decrease tissue oxygen tension. We and others have demonstrated that hypoxia is a potent stimulant for MSC (mesenchymal stem cell) recruitment and differentiation, yet to date little research has focused on the effects of oxygen tension on MSC migration. In the present study, we examined the effects of hypoxia and the potential role of the GTPase RhoA and HIF-1α (hypoxia-inducible factor 1α) on MSC migration. Our results demonstrate that hypoxia decreases MSC migration through an HIF-1α and RhoA-mediated pathway. The active GTP-bound form of RhoA was reduced in 1% oxygen, whereas activation of RhoA under hypoxic conditions rescued migration. Furthermore, stabilization of HIF-1α under normoxic conditions attenuated cell migration similar to that of hypoxia. These results suggest that hypoxia negatively affects MSC migration by regulating activation of GTPases. These results highlight the importance of oxygen in regulating the recruitment of progenitor cells to areas of ischaemic tissue damage. 相似文献