全文获取类型
收费全文 | 1123篇 |
免费 | 70篇 |
出版年
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 21篇 |
2020年 | 15篇 |
2019年 | 23篇 |
2018年 | 18篇 |
2017年 | 23篇 |
2016年 | 44篇 |
2015年 | 56篇 |
2014年 | 51篇 |
2013年 | 56篇 |
2012年 | 102篇 |
2011年 | 92篇 |
2010年 | 48篇 |
2009年 | 55篇 |
2008年 | 86篇 |
2007年 | 53篇 |
2006年 | 57篇 |
2005年 | 70篇 |
2004年 | 56篇 |
2003年 | 46篇 |
2002年 | 48篇 |
2001年 | 26篇 |
2000年 | 27篇 |
1999年 | 27篇 |
1998年 | 8篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 7篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 6篇 |
1990年 | 7篇 |
1989年 | 6篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1973年 | 2篇 |
1972年 | 1篇 |
排序方式: 共有1193条查询结果,搜索用时 281 毫秒
951.
The primo-vascular (Bonghan) tissue has been identified in most tissues in the body, but its structure and functions are not
yet well understood. We characterized electrophysiological properties of the cells of the primo-nodes (PN) on the surface
of abdominal organs using a slice patch clamp technique. The most abundant were small round cells (~10 μm) without processes.
These PN cells exhibited low resting membrane potential (−36 mV) and did not fire action potentials. On the basis of the current–voltage
(I–V) relationships and kinetics of outward currents, the PN cells can be grouped into four types. Among these, type I cells
were the majority (69%); they showed strong outward rectification in I–V relations. The outward current was activated rapidly
and sustained without decay. Tetraethylammonium (TEA) dose-dependently blocked both outward and inward current (IC50, 4.3 mM at ±60 mV). In current clamp conditions, TEA dose-dependently depolarized the membrane potential (18.5 mV at 30 mM)
with increase in input resistance. The tail current following a depolarizing voltage step was reversed at −27 mV, and transient
outward current like A-type K+ current was not expressed at holding potential of −80 mV. Taken together, the results demonstrate for the first time that
the small round PN cells are heterogenous, and that, in type I cells, TEA-sensitive current with limited selectivity to K+ contributed to resting membrane potential of these cells. 相似文献
952.
Asanuma M Kurokawa K Ichikawa R Ryu KH Chae JH Dohmae N Lee BL Nakayama H 《The FEBS journal》2011,278(5):716-728
Bacterial lipoproteins are known to be diacylated or triacylated and activate mammalian immune cells via Toll-like receptor 2/6 or 2/1 heterodimer. Because the genomes of low G+C content gram-positive bacteria, such as Staphylococcus aureus, do not contain Escherichia coli-type apolipoprotein N-acyltransferase, an enzyme converting diacylated lipoproteins into triacylated forms, it has been widely believed that native lipoproteins of S. aureus are diacylated. However, we recently demonstrated that one lipoprotein SitC purified from S. aureus RN4220 strain was triacylated. Almost simultaneously, another group reported that another lipoprotein SA2202 purified from S. aureus SA113 strain was diacylated. The determination of exact lipidated structures of S. aureus lipoproteins is thus crucial for elucidating the molecular basis of host-microorganism interactions. Toward this purpose, we intensively used MS-based analyses. Here, we demonstrate that SitC lipoprotein of S. aureus RN4220 strain has two lipoprotein lipase-labile O-esterified fatty acids and one lipoprotein lipase-resistant fatty acid. Further MS/MS analysis of the lipoprotein lipase digest revealed that the lipoprotein lipase-resistant fatty acid was acylated to α-amino group of the N-terminal cysteine residue of SitC. Triacylated forms of SitC with various length fatty acids were also confirmed in cell lysate of the RN4220 and Triton X-114 phase in three other S. aureus strains, including SA113 strain and one Staphylococcus epidermidis strain. Moreover, four other major lipoproteins including SA2202 in S. aureus strains were identified as N-acylated. These results strongly suggest that lipoproteins of S. aureus are mainly in the N-acylated triacyl form. 相似文献
953.
Background
In microarray data analysis, hierarchical clustering (HC) is often used to group samples or genes according to their gene expression profiles to study their associations. In a typical HC, nested clustering structures can be quickly identified in a tree. The relationship between objects is lost, however, because clusters rather than individual objects are compared. This results in a tree that is hard to interpret.Methodology/Principal Findings
This study proposes an ordering method, HC-SYM, which minimizes bilateral symmetric distance of two adjacent clusters in a tree so that similar objects in the clusters are located in the cluster boundaries. The performance of HC-SYM was evaluated by both supervised and unsupervised approaches and compared favourably with other ordering methods.Conclusions/Significance
The intuitive relationship between objects and flexibility of the HC-SYM method can be very helpful in the exploratory analysis of not only microarray data but also similar high-dimensional data. 相似文献954.
Wang AG Moon HB Chae JI Kim JM Kim YE Yu DY Lee DS 《Biochemical and biophysical research communications》2011,(3):532-538
Hepatic steatosis is considered to have an important impact on liver tumorigenesis, despite a lack of clear experimental evidence. Histopathological analysis of H-ras12V transgenic mice showed liver lesions on a steatosis background had significantly higher incidence than on a non-steatosis background. Further investigation showed that apolipoprotein A-I was elevated and accumulated around fatty vacuoles. This elevated level of apolipoprotein A-I was coupled with an elevated level of H-ras12V protein and ROS. In conclusion, our results suggest that the expression of H-ras12V oncogene leads to elevated levels of ROS and apolipoprotein A-I that contribute to steatosis. The steatosis, in turn, promotes the development of hepatic lesions induced by H-ras12V oncogene. 相似文献
955.
Recently, several flavonoids have been shown to have cardioprotective, cancer preventive, or anti-inflammatory properties. However, the specific mechanisms underlying their protective effects remain unclear. We aimed to investigate the different effects of three representative flavonoids—hesperidin, naringin, and resveratrol—on intracellular adhesion molecule-1 (ICAM-1) induction in human umbilical vein endothelial cells (HUVECs) by using high-glucose (HG) concentrations and the possible underlying molecular mechanisms. In HG-induced HUVEC cultures, the effects of three different flavonoids on ICAM-1 production and p38 phosphorylation were examined in the presence or absence of inhibitors targeting the mitogen-activated protein kinase (MAPK) signal transduction pathway. HG stimulation of HUVECs increased the levels of the adhesion molecules ICAM-1 and endothelial selectin (E-selectin). Pretreatment with all the three flavonoids drastically inhibited ICAM-1 expression in a time-dependent manner, but did not alter VCAM-1 and E-selectin expressions. Moreover, we investigated the effects of flavonoids on the MAPK signal transduction pathway, because MAPK families are associated with vascular inflammation under stress. These flavonoids did not block HG-induced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but completely inhibited the HG-induced phosphorylation of p38 MAPK. SB202190, an inhibitor of p38 MAPK, also inhibited the HG-induced enrichment of ICAM-1. This study demonstrated that hesperidin, naringin, and resveratrol reduced the HG-induced ICAM-1 expression via the p38 MAPK signaling pathway, contributing to the inhibition of monocyte adhesion to endothelial cells. 相似文献
956.
Kim BK Kim SU Kim HS Park JY Ahn SH Chon CY Cho IR Joh DH Park YN Han KH Kim do Y 《PloS one》2012,7(4):e35825
Background and Aims
Diagnostic values of FibroTest (FT) for hepatic fibrosis have rarely been assessed in Asian chronic hepatitis B (CHB) patients. We aimed to validate its diagnostic performances in comparison with liver stiffness (LS).Methods
From 2008 to 2010, 194 CHB patients who underwent liver biopsies along with FT and transient elastography were prospectively enrolled. Fibrosis stage was assessed according to the Batts and Ludwig system.Results
To predict significant fibrosis (F≥2), advanced fibrosis (F≥3), and cirrhosis (F = 4), areas under receiver operating characteristic curves (AUROCs) of FT were 0.903, 0.907, and 0.866, comparable to those of LS (0.873, 0.897, and 0.910, respectively). Optimized cutoffs of FT to maximize sum of sensitivity and specificity were 0.32, 0.52, and 0.68 for F≥2, F≥3, and F = 4, while those of LS were 8.8, 10.2, and 14.1 kPa, respectively. According to FT and LS cutoffs, 123 (63.4%) and 124 (63.9%) patients were correctly classified consistent with histological fibrosis (F1, F2, F3, and F4), respectively. Overall concordance between each fibrosis stage estimated by FT and LS was observed in 111 patients, where 88 were correctly classified with histological results. A combination formula adding LS to FT (LS+FT) showed similar AUROC levels (0.885, 0.905, and 0.915), while another multiplying LS by FT (LS×FT) showed the best AUROCs (0.941, 0.931, and 0.929 for F≥2, F≥3, and F4, respectively).Conclusions
FT provides good fibrosis prediction, with comparable outcomes to LS in Asian CHB patients. FT substantially reduces need for liver biopsy, especially when used in combination with LS. 相似文献957.
In this study, we reported on the design of a multiplex real-time PCR assay based on SYBR Green I, incorporating dual priming
adenine-thymine (AT)-rich primers for direct detection of MRSA from nasal samples. The multiplex real-time polymerase chain
reaction (RT-PCR) assay reported in this study is based on SYBR Green I with incorporation of six dual priming AT-rich primers
designed from the SCCmec/orf junction. A string (4–6 bp) of low-melting bases, such as adenine and thymine, was incorporated into the primers, which
virtually divided a single primer in two functional regions, thus decreasing non-specific PCR products. The analytical sensitivity
and specificity of the RT-PCR assay was determined with genomic DNA of reference strains (MRSA, MSSA, and MRCoNS). RT-PCR
assay was performed for analysis of 72 nasal swab specimens, and the results were confirmed by use of a culture method. Furthermore,
the results of RT-PCR were compared with LightCycler MRSA advance test. The multiplex RT-PCR assay reproducibly detected a
minimum of 1 pg genomic DNA (31.5 copy of genome) of MRSA reference strains and clinical isolates, with a specific melting
peak at 83.5 ± 1.5°C, and neither fluorescence nor a melting peak was detected in non-target isolates. The concordance rate
between RT-PCR assay and culture method was 87.5% with Cohen's kappa value (κ) 0.75, which showed good agreement between the two assays. The sensitivity, specificity, positive predictive value, and negative
predictive value of the assay were 93.5%, 82.9%, 80.5%, and 94.4%, respectively. In a comparative study for the detection
of 72 nasal samples, the sensitivity, specificity, positive predictive value, and negative predictive value of the multiplex
RT-PCR assay with respect to LightCycler MRSA advance test was 84.2%, 88.2%, 89%, and, 83.3%, respectively. The results of
RT-PCR assay demonstrated high specificity (88.2%) and positive predictive value (89%) for the direct detection of MRSA from
nasal samples. 相似文献
958.
Herbaspirillum sp. strain GW103 was isolated from rhizosphere soil of the reed Phragmites australis on reclaimed land. Here we report the 5.05-Mb draft genome sequence of the strain, providing bioinformation about the agronomic benefits of this strain, such as multiple traits relevant to plant root colonization and plant growth promotion. 相似文献
959.
960.