全文获取类型
收费全文 | 2658篇 |
免费 | 175篇 |
出版年
2022年 | 17篇 |
2021年 | 40篇 |
2020年 | 25篇 |
2019年 | 35篇 |
2018年 | 33篇 |
2017年 | 37篇 |
2016年 | 47篇 |
2015年 | 78篇 |
2014年 | 96篇 |
2013年 | 217篇 |
2012年 | 134篇 |
2011年 | 135篇 |
2010年 | 65篇 |
2009年 | 71篇 |
2008年 | 118篇 |
2007年 | 127篇 |
2006年 | 121篇 |
2005年 | 110篇 |
2004年 | 99篇 |
2003年 | 92篇 |
2002年 | 89篇 |
2001年 | 72篇 |
2000年 | 73篇 |
1999年 | 78篇 |
1998年 | 24篇 |
1997年 | 20篇 |
1994年 | 21篇 |
1993年 | 18篇 |
1992年 | 54篇 |
1991年 | 66篇 |
1990年 | 39篇 |
1989年 | 39篇 |
1988年 | 52篇 |
1987年 | 32篇 |
1986年 | 44篇 |
1985年 | 40篇 |
1984年 | 22篇 |
1983年 | 32篇 |
1982年 | 16篇 |
1981年 | 22篇 |
1980年 | 20篇 |
1979年 | 28篇 |
1978年 | 15篇 |
1977年 | 20篇 |
1975年 | 14篇 |
1974年 | 24篇 |
1973年 | 22篇 |
1972年 | 15篇 |
1971年 | 15篇 |
1968年 | 15篇 |
排序方式: 共有2833条查询结果,搜索用时 15 毫秒
121.
122.
Masaaki Konishi Seigo Sugiyama Koichi Sugamura Toshimitsu Nozaki Keisuke Ohba Junichi Matsubara Kenji Sakamoto Yasuhiro Nagayoshi Hitoshi Sumida Eiichi Akiyama Yasushi Matsuzawa Kentaro Sakamaki Satoshi Morita Kazuo Kimura Satoshi Umemura Hisao Ogawa 《PloS one》2013,8(4)
Background
Cardiac troponin is a specific biomarker for cardiomyocyte necrosis in acute coronary syndromes. Troponin release from the coronary circulation remains to be determined because of the lower sensitivity of the conventional assay. We sought to determine basal and angina-induced troponin release using a highly sensitive troponin assay.Methods and Results
The cardiac troponin T levels in serum sampled from the peripheral vein (PV), the aortic root (AO), and the coronary sinus (CS) were measured in 105 consecutive stable patients with coronary risk factor(s) and suspected coronary artery disease (CAD) and in 33 patients without CAD who underwent an acetylcholine provocation test. At baseline, there was a significant increase in the troponin levels from AO [9.0 (6.4, 13.1) pg/mL for median (25th, 75th percentiles)] to CS [10.3 (7.3, 15.5) pg/mL, p<0.001] in 96 (91.4%) patients and the difference was 1.1 (0.4, 2.1) pg/mL, which reflected basal transcardiac troponin release (TTR). TTR was positively correlated with PV levels (r = 0.22, p = 0.03). Male sex, left ventricular hypertrophy determined by echocardiography, T-wave inversion, and CAD correlated with elevated TTR defined as above: median, 1.1 pg/mL. A significant increase in TTR was noted in 17 patients with coronary spasms [0.6 (0.2, 1.2) pg/mL, p<0.01] but not in 16 patients without spasms [0.0 (−0.5, 0.9) pg/mL, p = 0.73] after the acetylcholine provocation.Conclusion
Basal TTR in the coronary circulation was observed in most of the patients with suspected CAD and risk factor(s). This sensitive assay detected myocardial ischemia-induced increases in TTR caused by coronary spasms. 相似文献123.
Daisuke Hayasaka Kenji Shirai Kotaro Aoki Noriyo Nagata Dash Sima Simantini Kazutaka Kitaura Yuki Takamatsu Ernest Gould Ryuji Suzuki Kouichi Morita 《PloS one》2013,8(8)
Japanese encephalitis virus (JEV) causes acute central nervous system (CNS) disease in humans, in whom the clinical symptoms vary from febrile illness to meningitis and encephalitis. However, the mechanism of severe encephalitis has not been fully elucidated. In this study, using a mouse model, we investigated the pathogenetic mechanisms that correlate with fatal JEV infection. Following extraneural infection with the JaOArS982 strain of JEV, infected mice exhibited clinical signs ranging from mild to fatal outcome. Comparison of the pathogenetic response between severe and mild cases of JaOArS982-infected mice revealed increased levels of TNF-α in the brains of severe cases. However, unexpectedly, the mortality rate of TNF-α KO mice was significantly increased compared with that of WT mice, indicating that TNF-α plays a protective role against fatal infection. Interestingly, there were no significant differences of viral load in the CNS between WT and TNF-α KO mice. However, exaggerated inflammatory responses were observed in the CNS of TNF-α KO mice. Although these observations were also obtained in IL-10 KO mice, the mortality and enhanced inflammatory responses were more pronounced in TNF-α KO mice. Our findings therefore provide the first evidence that TNF-α has an immunoregulatory effect on pro-inflammatory cytokines in the CNS during JEV infection and consequently protects the animals from fatal disease. Thus, we propose that the increased level of TNF-α in severe cases was the result of severe disease, and secondly that immunopathological effects contribute to severe neuronal degeneration resulting in fatal disease. In future, further elucidation of the immunoregulatory mechanism of TNF-α will be an important priority to enable the development of effective treatment strategies for Japanese encephalitis. 相似文献
124.
Jun-ichi Tsuboi Kentaro Morita Yusuke Koseki Shinsuke Endo Genki Sahashi Daisuke Kishi Takeshi Kikko Daisuke Ishizaki Masanori Nunokawa Yoichiro Kanno 《Oikos》2020,129(6):924-937
Animal populations are spatially structured in heterogeneous landscapes, in which local patches with differing vital rates are connected by dispersal of individuals to varying degrees. Although there is evidence that vital rates differ among local populations, much less is understood about how vital rates covary among local patches in spatially heterogeneous landscapes. In this study, we conducted a nine-year annual mark–recapture survey to characterize spatial covariation of survival and growth for two Japanese native salmonids, white-spotted charr Salvelinus leucomaenis japonicus and red-spotted masu salmon Oncorhynchus masou ishikawae, in a headwater stream network composed of distinctly different tributary and mainstem habitats. Spatial structure of survival and growth differed by species and age class, but results provided support for negative covariation between vital rates, where survival was higher in the tributary habitat but growth was higher in the mainstem habitat. Thus, neither habitat was apparently more important than the other, and local habitats with complementary vital rates may make this spatially structured population less vulnerable to environmental change (i.e. portfolio effect). Despite the spatial structure of vital rates and possibilities that fish can exploit spatially distributed resources, movement of fish was limited due partly to a series of low-head dams that prevented upstream movement of fish in the study area. This study shows that spatial structure of vital rates can be complex and depend on species and age class, and this knowledge is likely paramount to elucidating dynamics of spatially structured populations. 相似文献
125.
Masako Ishihara Keigo Morita Yuka Iguchi Kosuke Takaku Keisuke Takata Tadao Kitagawa 《Zeitschrift fur angewandte Ichthyologie》2020,36(5):668-674
An endangered tetraploid spined loach species, Cobitis takenoi (Cypriniformes: Cobitidae; hereafter called Tango loach) is known to inhabit only a single river in Kyoto Prefecture, Japan. Since Tango loach was discovered recently, in 2010, and only described in 2016, its morphology, ecology, and genetics are not well studied. Another tetraploid spined loach species Cobitis sp. BIWAE type A (hereafter, called Ohshima loach) inhabits the same river. The two loaches are reported as morphologically distinguishable from each other. Although the habitats of the two species in the river are segregated (Ohshima loach and Tango loach inhabit the upper and lower reaches, respectively), they overlap to a small degree in the boundary area. Recently, some individuals with morphological characteristics that are intermediate between the two species were found in the overlap zone. It was suspected that hybrids between the two species were produced since breeding seasons of the two species overlapped. To investigate whether the two species produce hybrids, we performed mitochondrial and nuclear DNA analyses on the unidentifiable individuals. Eight individuals unidentifiable to the species level collected in the river between 2017 and 2018 were examined and compared with the Tango and Ohshima loach species. Using mitochondrial DNA (mtDNA) cytochrome b analysis, we found that six individuals had mtDNA types identical to Tango loach and two individuals had mtDNA types identical to Ohshima loach. Furthermore, sequencing analysis of nuclear recombination activating gene 1 (RAG-1) revealed that each species had species-specific alleles. The phylogenetic analysis indicated that alleles in Tango loach were divided into two clusters and those from Ohshima loach formed a single cluster. There were no discrepancies in the combination between mtDNA and nuclear DNA species types within each specimen. DNA fingerprinting analysis (AFLP) showed that the species-unidentifiable individuals exhibited distinctly segregated genetic groups corresponding with Tango and Ohshima loaches. In summary, no hybrids were detected from among any unidentifiable individual examined in this study. New conventional genetic method for discriminating the two sympatric loach species developed here can be effective tool for the conservation of the Tango loach since there was no strict diagnostic morphological character between them. 相似文献
126.
Ayaka Furukawa Sumire Mitarai Mitsuhiro Takagi Yuuhei Yoshida Makoto Ozawa Akira Taneno Eisaburo Deguchi 《Microbiology and immunology》2020,64(5):387-391
Because broad genetic diversity has recently been detected in Torque teno sus viruses (TTSuV1 and TTSuVk2), the viral genome detection method needs to be improved to understand the prevalence of these viruses. Here, we established single PCR-based detection methods for the TTSuV1 and TTSuVk2a genomes with newly designed primer pairs and applied them to investigate the prevalence of TTSuV1 and TTSuVk2a in Japanese pig populations. The results revealed that 98.2% and 81.7% of the pig farms tested positive for the TTSuV1 and TTSuVk2a genomes, respectively, indicating that both TTSuV1 and TTSuVk2a are widespread in Japan. 相似文献
127.
Hayuki Sugimoto Yuichi Nakajima Ayaka Motoyama Erina Katagiri Takeshi Watanabe Kazushi Suzuki 《Biopolymers》2020,111(1):e23339
Chitin-binding protein 21 (CBP21) from Serratia marcescens is a lytic polysaccharide monooxygenase that contains a copper ion as a cofactor. We aimed to elucidate the unfolding mechanism of CBP21 and the effects of Cu2+ on its structural stability at pH 5.0. Thermal unfolding of both apo- and holoCBP21 was reversible. ApoCBP21 unfolded in a simple two-state transition manner. The peak temperature of the DSC curve, tp, for holoCBP21 (74.4°C) was about nine degrees higher than that for apoCBP21 (65.6°C). The value of tp in the presence of excess Cu2+ was around 75°C, indicating that Cu2+ does not dissociate from the protein molecule during unfolding. The unfolding mechanism of holoCBP21 was considered to be as follows: N∙Cu2+ ⇌ U∙Cu2+, where N and U represent the native and unfolded states, respectively. Urea-induced equilibrium unfolding analysis showed that holoCBP21 was stabilized by 35 kJ mol−1 in terms of the Gibbs energy change for unfolding (pH 5.0, 25°C), compared with apoCBP21. The increased stability of holoCBP21 was considered to result from the structural stabilization of the protein-Cu2+ complex itself. 相似文献
128.
Vagner Oliveira-Carvalho Miguel Morita Fernandes da Silva Guilherme Veiga Guimarães Fernando Bacal Edimar Alcides Bocchi 《Molecular biology reports》2013,40(3):2663-2670
MicroRNAs (miRNAs) are a class of non-coding small RNAs representing one of the most exciting areas of modern medical science. miRNAs modulate a large and complex regulatory network of gene expression of the majority of the protein-coding genes. Currently, evidences suggest that miRNAs play a crucial role in the pathogenesis of heart failure. Some miRNAs as miR-1, miR-133 and miR-208a are highly expressed in the heart and strongly associated with the development of cardiac hypertrophy. Recent data indicate that these miRNAs as well as miR-206 change their expression quickly in response to physical activity. The differential regulation of miRNAs in response to exercise suggests a potential value of circulating miRNAs (c-miRNAs) as biomarkers of physiological mediators of the cardiovascular adaptation induced by exercise. Likewise, serum levels of c-miRNAs such as miR-423-5p have been evaluated as potential biomarkers in the diagnosis and prognosis of heart failure. On the other hand, the manipulation of miRNAs levels using techniques such as ‘miR mimics’ and ‘antagomiRs’ is becoming evident the enormous potential of miRNAs as promising therapeutic strategies in heart failure. 相似文献
129.
Hiroshi Katoh Toru Okamoto Takasuke Fukuhara Hiroto Kambara Eiji Morita Yoshio Mori Wataru Kamitani Yoshiharu Matsuura 《Journal of virology》2013,87(1):489-502
Stress granules (SGs) are cytoplasmic foci composed of stalled translation preinitiation complexes induced by environmental stress stimuli, including viral infection. Since viral propagation completely depends on the host translational machinery, many viruses have evolved to circumvent the induction of SGs or co-opt SG components. In this study, we found that expression of Japanese encephalitis virus (JEV) core protein inhibits SG formation. Caprin-1 was identified as a binding partner of the core protein by an affinity capture mass spectrometry analysis. Alanine scanning mutagenesis revealed that Lys97 and Arg98 in the α-helix of the JEV core protein play a crucial role in the interaction with Caprin-1. In cells infected with a mutant JEV in which Lys97 and Arg98 were replaced with alanines in the core protein, the inhibition of SG formation was abrogated, and viral propagation was impaired. Furthermore, the mutant JEV exhibited attenuated virulence in mice. These results suggest that the JEV core protein circumvents translational shutoff by inhibiting SG formation through an interaction with Caprin-1 and facilitates viral propagation in vitro and in vivo. 相似文献
130.