全文获取类型
收费全文 | 422篇 |
免费 | 37篇 |
出版年
2021年 | 6篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2017年 | 6篇 |
2016年 | 8篇 |
2015年 | 14篇 |
2014年 | 19篇 |
2013年 | 15篇 |
2012年 | 18篇 |
2011年 | 23篇 |
2010年 | 19篇 |
2009年 | 17篇 |
2008年 | 21篇 |
2007年 | 16篇 |
2006年 | 12篇 |
2005年 | 14篇 |
2004年 | 19篇 |
2003年 | 13篇 |
2002年 | 17篇 |
2001年 | 13篇 |
2000年 | 17篇 |
1999年 | 13篇 |
1998年 | 10篇 |
1997年 | 4篇 |
1996年 | 8篇 |
1995年 | 5篇 |
1994年 | 7篇 |
1993年 | 6篇 |
1992年 | 6篇 |
1991年 | 9篇 |
1990年 | 5篇 |
1989年 | 10篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1984年 | 3篇 |
1981年 | 3篇 |
1979年 | 2篇 |
1978年 | 6篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1968年 | 8篇 |
1967年 | 4篇 |
1966年 | 3篇 |
1965年 | 3篇 |
1963年 | 2篇 |
1959年 | 2篇 |
排序方式: 共有459条查询结果,搜索用时 375 毫秒
41.
Guy R Sander Simon J H Brookes Barry C Powell 《The journal of histochemistry and cytochemistry》2003,51(7):969-972
The Notch signaling pathway is a vitally important pathway in regulating brain development. To explore the involvement of the Notch pathway in neuronal cells of adult rat gut, we investigated the expression of Notch1 and Jagged2 by in situ hybridization (ISH) and immunohistochemistry (IHC). In the enteric nervous system, Notch1 and Jagged2 were expressed in ganglia of the submucosal and myenteric plexus. Notch1 was preferentially expressed in cholinergic neurons lacking calretinin or nitric oxide synthase (NOS), whereas Jagged2 was present in most neuron subtypes. We propose that Notch1 and Jagged2 have a continuing role in the maintenance and function of neuronal cells in the adult enteric nervous system. 相似文献
42.
Brunsden AM Brookes SJ Bardhan KD Grundy D 《American journal of physiology. Gastrointestinal and liver physiology》2007,293(2):G422-G428
Spinal afferent neurons, with endings in the intestinal mesenteries, have been shown to respond to changes in vascular perfusion rates. The mechanisms underlying this sensitivity were investigated in an in vitro preparation of the mesenteric fan devoid of connections with the gut wall. Afferent discharge increased when vascular perfusion was stopped ("flow off"), a response localized to the terminal vessels just prior to where they entered the gut wall. The flow-off response was compared following pharmacological manipulations designed to determine direct mechanical activation from indirect mechanisms via the vascular endothelium or muscle. Under Ca(2+)-free conditions, responses to flow off were significantly augmented. In contrast, the myosin light chain kinase inhibitor wortmannin (1 microM, 20 min) did not affect the flow-off response despite blocking the vasoconstriction evoked by 10 microM l-phenylephrine. This ruled out active tension, generated by vascular smooth muscle, in the response to flow off. Passive changes caused by vessel collapse during flow off were speculated to affect sensory nerve terminals directly. The flow-off response was not affected by the N-, P-, and Q-type Ca(2+) channel blocker omega-conotoxin MVIIC (1 muM intra-arterially) or the P2X receptor/ion channel blocker PPADS (50 microM). However, ruthenium red (50 microM), a blocker of nonselective cation channels, greatly reduced the flow-off response and also abolished the vasodilator response to capsaicin. Our data support the concept that mesenteric afferents sense changes in vascular flow during flow off through direct mechanisms, possibly involving nonselective cation channels. Passive distortion in the fan, caused by changes in blood flow, may represent a natural stimulus for these afferents in vivo. 相似文献
43.
44.
Mechanism of a plastic phenotypic response: predator-induced shell thickening in the intertidal gastropod Littorina obtusata 总被引:1,自引:0,他引:1
Phenotypic plasticity has been the object of considerable interest over the past several decades, but in few cases are mechanisms underlying plastic responses well understood. For example, it is unclear whether predator-induced changes in gastropod shell morphology represent an active physiological response or a by-product of reduced feeding. We address this question by manipulating feeding and growth of intertidal snails, Littorina obtusata, using two approaches: (i) exposure to predation cues from green crabs Carcinus maenas and (ii) reduced food availability, and quantifying growth in shell length, shell mass, and body mass, as well as production of faecal material and shell micro-structural characteristics (mineralogy and organic fraction) after 96 days. We demonstrate that L. obtusata actively increases calcification rate in response to predation threat, and that this response entails energetic and developmental costs. That this induced response is not strictly tied to the animal's behaviour should enhance its evolutionary potential. 相似文献
45.
Sylvia Kamphuis Kolbrún Hrafnkelsdóttir Mark R Klein Wilco de Jager Margje H Haverkamp Jolanda HM van Bilsen Salvatore Albani Wietse Kuis Marca HM Wauben Berent J Prakken 《Arthritis research & therapy》2007,8(6):R178
Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease characterized by chronic joint inflammation. Knowing
which antigens drive the autoreactive T-cell response in JIA is crucial for the understanding of disease pathogenesis and
additionally may provide targets for antigen-specific immune therapy. In this study, we tested 9 self-peptides derived from
joint-related autoantigens for T-cell recognition (T-cell proliferative responses and cytokine production) in 36 JIA patients
and 15 healthy controls. Positive T-cell proliferative responses (stimulation index ≥2) to one or more peptides were detected
in peripheral blood mononuclear cells (PBMC) of 69% of JIA patients irrespective of major histocompatibility complex (MHC)
genotype. The peptides derived from aggrecan, fibrillin, and matrix metalloproteinase (MMP)-3 yielded the highest frequency
of T-cell proliferative responses in JIA patients. In both the oligoarticular and polyarticular subtypes of JIA, the aggrecan
peptide induced T-cell proliferative responses that were inversely related with disease duration. The fibrillin peptide, to
our knowledge, is the first identified autoantigen that is primarily recognized in polyarticular JIA patients. Finally, the
epitope derived from MMP-3 elicited immune responses in both subtypes of JIA and in healthy controls. Cytokine production
in short-term peptide-specific T-cell lines revealed production of interferon-γ (aggrecan/MMP-3) and interleukin (IL)-17 (aggrecan)
and inhibition of IL-10 production (aggrecan). Here, we have identified a triplet of self-epitopes, each with distinct patterns
of T-cell recognition in JIA patients. Additional experiments need to be performed to explore their qualities and role in
disease pathogenesis in further detail. 相似文献
46.
47.
48.
49.
John W. Arkwright Neil G. Blenman Ian D. Underhill Simon A. Maunder Nicholas J. Spencer Marcello Costa Simon J. Brookes Michael M. Szczesniak Phil G. Dinning 《Journal of biophotonics》2011,4(4):244-251
Diagnostic catheters based on fibre Bragg gratings (FBG's) are proving to be highly effective for measurement of the muscular activity associated with motility in the human gut. While the primary muscular contractions that generate peristalsis are circumferential in nature, it has long been known that there is also a component of longitudinal contractility present, acting in harmony with the circumferential component to improve the overall efficiency of material movement. We report the detection of longitudinal motion in mammalian intestine using an FBG technique that should be viable for similar detection in humans. The longitudinal sensors have been combined with our previously reported FBG pressure sensing elements to form a composite catheter that allows the relative phase between the two components to be detected. The catheter output has been validated using video mapping in an ex‐vivo rabbit ileum preparation. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
50.
Lindström S Wiklund F Jonsson BA Adami HO Bälter K Brookes AJ Xu J Zheng SL Isaacs WB Adolfsson J Grönberg H 《Human genetics》2005,118(3-4):339-347
The E-cadherin gene (CDH1) has been proposed as a prostate cancer (PC) susceptibility gene in several studies. Aberrant protein expression has been related to prognosis and progression in PC. In addition, a functional promoter SNP (rs16260) has been found to associate with PC risk. We performed a comprehensive genetic analysis of CDH1 by using the method of haplotype tagged SNPs in a large Swedish population-based case-control study consisting of 801 controls and 1,636 cases. In addition, Swedish PC families comprising a total of 157 cases sampled for DNA were analyzed for selected SNPs. Seven SNPs, including the promoter SNP rs16260, that captured over 96% of CDH1 haplotype variation were selected as haplotype tagging SNPs and analyzed for associated PC risk. We observed significant confirmation of rs16260 (P=0.003) for cases with a positive family history of PC (FH+) both in an independent case-control population and in PC families. In addition, a common haplotype (HapB, 25%) including the variant allele of rs16260 was associated (P=0.004) with PC risk among FH+ cases. The promoter SNP rs16260 as well as HapB were significantly transmitted to affected offspring in PC families. We report strong confirmation of the association between PC risk in FH+ cases and a functional CDH1 promoter SNP in an independent population. In conjunction with the biological importance of CDH1 our findings encourage further evaluation of genetic variation in CDH1 in relation to PC etiology. Due to the difficulties in replication of genetic association studies, this finding is unusual and novel. 相似文献