全文获取类型
收费全文 | 1009篇 |
免费 | 55篇 |
出版年
2024年 | 1篇 |
2023年 | 7篇 |
2022年 | 11篇 |
2021年 | 31篇 |
2020年 | 16篇 |
2019年 | 14篇 |
2018年 | 29篇 |
2017年 | 27篇 |
2016年 | 42篇 |
2015年 | 64篇 |
2014年 | 76篇 |
2013年 | 79篇 |
2012年 | 91篇 |
2011年 | 88篇 |
2010年 | 55篇 |
2009年 | 32篇 |
2008年 | 74篇 |
2007年 | 66篇 |
2006年 | 35篇 |
2005年 | 39篇 |
2004年 | 48篇 |
2003年 | 35篇 |
2002年 | 39篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 9篇 |
1998年 | 13篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 8篇 |
1994年 | 2篇 |
1993年 | 7篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有1064条查询结果,搜索用时 15 毫秒
311.
Collins-Fairclough AM Charurat M Nadai Y Pando M Avila MM Blattner WA Carr JK 《PloS one》2011,6(6):e19995
Background
In Trinidad and the wider Caribbean, subtype B Human Immunodeficiency Virus-type 1 (HIV-1B) overwhelmingly accounts for HIV infection among heterosexuals; this contrasts with the association of HIV-1B with homosexual transmission and injecting drug use globally. The HIV envelope contains genetic determinants of cell tropism and evasion from immune attack. In this study we investigate the genetic properties of the env V1-C4 of HIV-1B soon after transmission to Trinidadian heterosexuals. This will reveal distinctive genetic features of the strains that cause the HIV-1B epidemic in Trinidad and generate insights to better understand their properties.Methodology/Principal Findings
Quasispecies sampling was performed on the env V1-C4 of HIV-1B strains soon after transmission to heterosexual Trinidadians in a cohort of seroconverters. Phylogenetic relationships were determined for these quasispecies and the length and number of asparagine (N) linked glycosylation sites (NLGS) in their variable loops compared to that for HIV-1B globally. Signature amino acids within the constant domains of the env V1-C4 were identified for heterosexually transmitted HIV-1B from Trinidad relative to HIV-1B globally. HIV-1B obtained from Trinidadian heterosexuals soon after seroconversion had significantly longer V2 loops with one more glycosylation site, shorter V3 loops and no significant difference in V1 or V4 when compared to HIV-1B obtained soon after seroconversion from infected individuals in the rest of the world. HIV-1B soon after seroconversion and during chronic infection of Trinidadians was not significantly different, suggesting that distinctly long V2 loops are characteristic of HIV-1B in Trinidad. A threonine deletion at position 319 (T319-) along with the substitutions R315K and S440R were found to be distinctly associated with HIV-1B from Trinidad compared to HIV-1B globally.Conclusions
This finding of distinctive genetic features that are characteristic of HIV-1B strains from Trinidad is consistent with the Trinidad epidemic being established by a founder strain or closely related founder strains of HIV-1B. 相似文献312.
313.
Saori Morino‐Koga Shuichiro Yano Tatsuya Kondo Yuichiro Shimauchi Shingo Matsuyama Yuka Okamoto Mary Ann Suico Tomoaki Koga Takashi Sato Tsuyoshi Shuto Hidetoshi Arima Ikuo Wada Eiichi Araki Hirofumi Kai 《Journal of cellular physiology》2013,228(2):439-446
Insulin resistance is due to the reduced cellular response to insulin in peripheral tissues. The interaction of insulin with its receptor is the first step in insulin action and thus the identified target of insulin resistance. It has been well established that defects or mutations in the insulin receptor (IR) cause insulin resistance. Therefore, an IR activator might be a novel therapeutic approach for insulin resistance. Our previous report showed that mild electrical stress (MES) enhanced the insulin‐induced signaling pathway. However, the molecular mechanism of the effect of MES remains unclear. We assessed the effect of MES, which is characterized by low‐intensity direct current, on insulin signaling in vitro and in vivo. Here, we showed that MES activated the insulin signaling in an insulin‐independent manner and improved insulin resistance in peripheral tissues of high fat‐fed mice. Moreover, we found that MES increased the localization of IR in lipid rafts and enhanced the level of phosphorylated Akt in insulin‐resistant hepatic cells. Ablation of lipid rafts disrupted the effect of MES on Akt activation. Our findings indicate that MES has potential as an activator of IR in an insulin‐independent manner, and might be beneficial for insulin resistance in type 2 diabetes. J. Cell. Physiol. 228: 439–446, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
314.
Jumpei Ito Shinya Watanabe Takahiro Hiratsuka Kyohei Kuse Yuka Odahara Haruyo Ochi Maki Kawamura Kazuo Nishigaki 《Journal of virology》2013,87(22):12029-12040
The host defense against viral infection is acquired during the coevolution or symbiosis of the host and pathogen. Several cellular factors that restrict retroviral infection have been identified in the hosts. Feline leukemia virus (FeLV) is a gammaretrovirus that is classified into several receptor interference groups, including a novel FeLV-subgroup D (FeLV-D) that we recently identified. FeLV-D is generated by transduction of the env gene of feline endogenous gammaretrovirus of the domestic cat (ERV-DCs) into FeLV. Some ERV-DCs are replication competent viruses which are present and hereditary in cats. We report here the determination of new viral receptor interference groups and the discovery of a soluble antiretroviral factor, termed Refrex-1. Detailed analysis of FeLV-D strains and ERV-DCs showed two receptor interference groups that are distinct from other FeLV subgroups, and Refrex-1 specifically inhibited one of them. Refrex-1 is characterized as a truncated envelope protein of ERV-DC and includes the N-terminal region of surface unit, which is a putative receptor-binding domain, but lacks the transmembrane region. Refrex-1 is efficiently secreted from the cells and appears to cause receptor interference extracellularly. Two variants of Refrex-1 encoded by provirus loci, ERV-DC7 and DC16, are expressed in a broad range of feline tissues. The host retains Refrex-1 as an antiretroviral factor, which may potentially prevent reemergence of the ERVs and the emergence of novel ERV-related viruses in cats. Refrex-1 may have been acquired during endogenization of ERV-DCs and may play an important role in retroviral restriction and antiviral defense in cats. 相似文献
315.
316.
Takao Mukuda Sawako Hamasaki Yuka Koyama Yoshio Takei Toshiyuki Kaidoh Takao Inoué 《Cell and tissue research》2013,353(3):525-538
Systemic angiotensin II (Ang II) is a dipsogen in terrestrial vertebrates and seawater teleosts. In eels, Ang II acts on the area postrema, a sensory circumventricular organ (CVO) and elicits water intake but other sensory CVOs have not yet been found in the eel forebrain. To identify sensory CVOs in the forebrain, eels were peripherally injected with Evans blue, which immediately binds to albumin, or a rabbit IgG protein. Extravasation of these proteins, which cannot cross the blood–brain barrier (BBB), was observed in the brain parenchyma of the anteroventral preoptic recess (PR) walls. Fenestrated capillaries were observed in the parenchymal margin of the ventral wall of the PR, confirming a deficit of the BBB in the eel forebrain. Immunostaining for tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) detected neurons in the lateral region of the anterior parvocellular preoptic nucleus (PPa), which were strongly stained by BBB-impermeable N-hydroxysulfosuccinimide. In the periventricular region of the PPa, many neurons incorporated biotinylated dextran amine conjugated to fluorescein, a retrograde axonal tracer, injected into the magnocellular preoptic nucleus (PM), indicating neuronal connections from the PPa to the PM. The mammalian paraventricular and supraoptic nuclei, homologous to the teleost PM, receive principal neuronal projections from the organum vasculosum of the lamina terminalis (OVLT). These results strongly suggest that the periventricular subpopulation of the PPa, which is most likely to be a component of the OVLT, serves as a functional window of access for systemic signal molecules such as Ang II. 相似文献
317.
Tomohito Matsuo Yukiko Noguchi Mieko Shindo Yoshifumi Morita Yoshie Oda Eiko Yoshida Hiroko Hamada Mine Harada Yuichi Shiokawa Takahiro Nishida Ryuji Tominaga Yoshikane Kikushige Koichi Akashi Jun Kudoh Nobuyoshi Shimizu Yuka Tanaka Tsukuru Umemura Taketoshi Taniguchi Akihiko Yoshimura Takashi Kobayashi Masao Mitsuyama Hironori Kurisaki Hitoshi Katsuta Seiho Nagafuchi 《Gene》2013
Although mutations of autoimmune regulator (AIRE) gene are responsible for autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), presenting a wide spectrum of many characteristic and non-characteristic clinical features, some patients lack AIRE gene mutations. Therefore, something other than a mutation, such as dysregulation of AIRE gene, may be a causal factor for APECED or its related diseases. However, regulatory mechanisms for AIRE gene expression and/or translation have still remained elusive. We found that IL-2-stimulated CD4+ T (IL-2T) cells showed a high expression of AIRE gene, but very low AIRE protein production, while Epstein–Barr virus-transformed B (EBV-B) cells express both AIRE gene and AIRE protein. By using microarray analysis, we could identify miR-220b as a possible regulatory mechanism for AIRE gene translation in IL-2T cells. Here we report that miR-220b significantly reduced the expression of AIRE protein in AIRE gene with 3′UTR region transfected 293T cells, whereas no alteration of AIRE protein production was observed in the open reading frame of AIRE gene alone transfected cells. In addition, anti-miR-220b reversed the inhibitory function of miR-220b for the expression of AIRE protein in AIRE gene with 3′UTR region transfected cells. Moreover, when AIRE gene transfected cells with mutated 3′UTR were transfected with miR-220b, no reduction of AIRE protein production was observed. Taken together, it was concluded that miR-220b inhibited the AIRE gene translation through the 3′UTR region of AIRE gene, indicating that miR-220b could serve as a regulator for human AIRE gene translation. 相似文献
318.
319.
Kimihiko Murase Kiyoshi Mori Chikara Yoshimura Kensaku Aihara Yuichi Chihara Masanori Azuma Yuka Harada Yoshiro Toyama Kiminobu Tanizawa Tomohiro Handa Takefumi Hitomi Toru Oga Michiaki Mishima Kazuo Chin 《PloS one》2013,8(1)
Background
Both obstructive sleep apnea (OSA) and a novel lipocalin, neutrophil gelatinase associated lipocalin (Ngal), have been reported to be closely linked with cardiovascular disease and loss of kidney function through chronic inflammation. However, the relationship between OSA and Ngal has never been investigated.Objectives
To evaluate the relationship between Ngal and OSA in clinical practice.Methods
In 102 patients, polysomnography was performed to diagnose OSA and plasma Ngal levels were measured. The correlations between Ngal levels and OSA severity and other clinical variables were evaluated. Of the 46 patients who began treatment with continuous positive airway pressure (CPAP), Ngal levels were reevaluated after three months of treatment in 25 patients.Results
The Ngal level correlated significantly with OSA severity as determined by the apnea hypopnea index (r = 0.24, p = 0.01) and 4% oxygen desaturation index (ODI) (r = 0.26, p = 0.01). Multiple regression analysis showed that the Ngal level was associated with 4%ODI independently of other clinical variables. Compliance was good in 13 of the 25 patients who used CPAP. Although the OSA (4%ODI: 33.1±16.7 to 1.1±1.9/h, p<0.01) had significantly improved in those with good compliance, the Ngal levels were not significantly changed (60.5±18.1 before CPAP vs 64.2±13.9 ng/ml after CPAP, p = 0.27).Conclusions
Plasma Ngal levels were positively associated with the severity of OSA. However, the contribution rate of OSA to systemic Ngal secretion was small and changes in Ngal levels appeared to be influenced largely by other confounding factors. Therefore, it does not seem reasonable to use the Ngal level as a specific biomarker of OSA in clinical practice. 相似文献320.
When two tones are presented in a short time interval, the response to the second tone is suppressed. This phenomenon is referred to as forward suppression. To address the effect of the masker laterality on forward suppression, magnetoencephalographic responses were investigated for eight subjects with normal hearing when the preceding maskers were presented ipsilaterally, contralaterally, and binaurally. We employed three masker intensity conditions: the ipsilateral-strong, left-right-balanced, and contralateral-strong conditions. Regarding the responses to the maskers without signal, the N1m amplitude evoked by the left and binaural maskers was significantly larger than that evoked by the right masker for the left-strong and left-right-balanced conditions. No significant difference was observed for the right-strong condition. Regarding the subsequent N1m amplitudes, they were attenuated by the presence of the left, binaural, and right maskers for all conditions. For the left- and right-strong conditions, the subsequent N1m amplitude in the presence of the left masker was smaller than those of the binaural and right maskers. No difference was observed between the binaural and right masker presentation. For left-right-balanced condition, the subsequent N1m amplitude decreased in the presence of the right, binaural, and left maskers in that order. If the preceding activity reflected the ability to suppress the subsequent activity, the forward suppression by the left masker would be superior to that by the right masker for the left-strong and left-right-balanced conditions. Furthermore, the forward suppression by the binaural masker would be expected to be superior to that by the left masker owing to additional afferent activity from the right ear. Thus, the current results suggest that the forward suppression by ipsilateral maskers is superior to that by contralateral maskers although both maskers evoked the N1m amplitudes to the same degree. Additional masker at the contralateral ear can attenuate the forward suppression by the ipsilateral masker. 相似文献