全文获取类型
收费全文 | 1556篇 |
免费 | 100篇 |
出版年
2023年 | 8篇 |
2021年 | 16篇 |
2020年 | 7篇 |
2019年 | 16篇 |
2018年 | 15篇 |
2017年 | 13篇 |
2016年 | 27篇 |
2015年 | 43篇 |
2014年 | 56篇 |
2013年 | 83篇 |
2012年 | 74篇 |
2011年 | 76篇 |
2010年 | 57篇 |
2009年 | 44篇 |
2008年 | 83篇 |
2007年 | 80篇 |
2006年 | 84篇 |
2005年 | 74篇 |
2004年 | 60篇 |
2003年 | 78篇 |
2002年 | 55篇 |
2001年 | 55篇 |
2000年 | 55篇 |
1999年 | 50篇 |
1998年 | 16篇 |
1997年 | 19篇 |
1996年 | 15篇 |
1995年 | 14篇 |
1994年 | 10篇 |
1993年 | 15篇 |
1992年 | 38篇 |
1991年 | 47篇 |
1990年 | 27篇 |
1989年 | 29篇 |
1988年 | 22篇 |
1987年 | 22篇 |
1986年 | 25篇 |
1985年 | 19篇 |
1984年 | 17篇 |
1983年 | 19篇 |
1982年 | 9篇 |
1981年 | 9篇 |
1979年 | 5篇 |
1977年 | 12篇 |
1976年 | 5篇 |
1975年 | 10篇 |
1974年 | 9篇 |
1973年 | 5篇 |
1968年 | 5篇 |
1966年 | 4篇 |
排序方式: 共有1656条查询结果,搜索用时 15 毫秒
81.
82.
Beckstrom-Sternberg SM Auerbach RK Godbole S Pearson JV Beckstrom-Sternberg JS Deng Z Munk C Kubota K Zhou Y Bruce D Noronha J Scheuermann RH Wang A Wei X Wang J Hao J Wagner DM Brettin TS Brown N Gilna P Keim PS 《PloS one》2007,2(9):e947
Francisella tularensis is the causative agent of tularemia, which is a highly lethal disease from nature and potentially from a biological weapon. This species contains four recognized subspecies including the North American endemic F. tularensis subsp. tularensis (type A), whose genetic diversity is correlated with its geographic distribution including a major population subdivision referred to as A.I and A.II. The biological significance of the A.I - A.II genetic differentiation is unknown, though there are suggestive ecological and epidemiological correlations. In order to understand the differentiation at the genomic level, we have determined the complete sequence of an A.II strain (WY96-3418) and compared it to the genome of Schu S4 from the A.I population. We find that this A.II genome is 1,898,476 bp in size with 1,820 genes, 1,303 of which code for proteins. While extensive genomic variation exists between "WY96" and Schu S4, there is only one whole gene difference. This one gene difference is a hypothetical protein of unknown function. In contrast, there are numerous SNPs (3,367), small indels (1,015), IS element differences (7) and large chromosomal rearrangements (31), including both inversions and translocations. The rearrangement borders are frequently associated with IS elements, which would facilitate intragenomic recombination events. The pathogenicity island duplicated regions (DR1 and DR2) are essentially identical in WY96 but vary relative to Schu S4 at 60 nucleotide positions. Other potential virulence-associated genes (231) varied at 559 nucleotide positions, including 357 non-synonymous changes. Molecular clock estimates for the divergence time between A.I and A.II genomes for different chromosomal regions ranged from 866 to 2131 years before present. This paper is the first complete genomic characterization of a member of the A.II clade of Francisella tularensis subsp. tularensis. 相似文献
83.
Kouichi Kawamura Masashi Kubota Miki Furukawa Yasushi Harada 《Conservation Genetics》2007,8(5):1163-1176
The amago salmon, Oncorhynchus masou ishikawae, is an endemic subspecies of O. masou in Japan. Owing to the extensive stocking of hatchery fish throughout Japan, indigenous populations of O. m. ishikawae are now on the verge of extinction. We examined the genetic effects of stocking hatchery fish on wild populations in the
River Koza, Japan, using microsatellite and mitochondrial DNA (mtDNA) markers. For mtDNA, haplotype mt1, which is common in
wild populations, was present exclusively in isolated wild populations assumed to be unaffected by previous stocking, while
it was never observed in hatchery fish. Genetic diversity was much higher in wild populations in the stocked area, which shared
many mtDNA haplotypes with hatchery fish, than in isolated wild populations with haplotype mt1. Pairwise F
ST estimates based on microsatellites showed significant differentiation among the isolated populations with many microsatellite
loci monomorphic. Significant deviation from Hardy–Weinberg equilibrium was observed in wild populations in the area subject
to stocking, where a Bayesian-based assignment test showed a high level of introgression with hatchery fish. These results
suggest that wild populations with haplotype mt1, which became isolated through anthropogenic environmental change in the
1950–1960s, represent indigenous populations of O. m. ishikawae in the River Koza. They have low genetic diversity, most likely caused by genetic bottlenecks following damming and environmental
deterioration, while stocking of hatchery fish over the past 30 years apparently had a large impact on the genetic structure
of wild populations in the main channel of the River Koza. 相似文献
84.
G. Harata F. He N. Hiruta M. Kawase A. Kubota M. Hiramatsu H. Yausi 《Letters in applied microbiology》2010,50(6):597-602
Aims: To investigate whether intranasal Lactobacillus administration protects host animals from influenza virus (IFV) infection by enhancing respiratory immune responses in a mouse model. Methods and Results: After 3 days of intranasal exposure to Lactobacillus rhamnosus GG (LGG), BALB/c mice were infected with IFV A/PR/8/34 (H1N1). Mice treated with LGG showed a lower frequency of accumulated symptoms and a higher survival rate than control mice (P < 0·05). The YAC‐1 cell‐killing activity of lung cells isolated from mice treated with LGG was significantly greater than those isolated from control mice (P < 0·01). Intranasal administration of LGG significantly increased mRNA expression of interleukin (IL)‐1β, tumour necrosis factor (TNF) and monocyte chemotactic protein (MCP)‐1 (P < 0·01). Conclusions: These results suggest that intranasal administration of LGG protects the host animal from IFV infection by enhancing respiratory cell‐mediated immune responses following up‐regulation of lung natural killer (NK) cell activation. Significance and Impact of Study: We have demonstrated that probiotics might protect host animals from viral infection by stimulating immune responses in the respiratory tract. 相似文献
85.
Yohei Takahashi Haruaki Ishiyama Takaaki Kubota Jun’ichi Kobayashi 《Bioorganic & medicinal chemistry letters》2010,20(14):4100-4103
A new β-carboline alkaloid, eudistomidin G (1), has been isolated from the Okinawan marine tunicate Eudistoma glaucus, and the structure was elucidated from spectroscopic data. Furthermore, the structure of eudistomidin B (2), which has been isolated from the same tunicate, was revised from 2a to 2b by detailed analyses of spectroscopic data. Asymmetric synthesis of the revised structure (2b) of eudistomidin B (2) and its (1S,10S)-diastereomer (2c) has been accomplished with the Noyori catalytic asymmetric hydrogen-transfer reaction. The absolute configuration of eudistomidin B (2) was confirmed to be 2b possessing (1R,10S)-configuration, from comparison of the 1H NMR data, CD spectra, [α]D values, and HPLC analysis of 2b, 2c, and natural eudistomidin B. 相似文献
86.
Matrix metalloproteinase-2 and -9 in bile as a marker of liver metastasis in colorectal cancer 总被引:5,自引:0,他引:5
Okada N Ishida H Murata N Hashimoto D Seyama Y Kubota S 《Biochemical and biophysical research communications》2001,288(1):212-216
Matrix metallproteinases (MMP)-2 and -9 are associated with cancer invasion and metastasis. MMP-2 and MMP-9 activities have never been assayed in bile. In the present study we investigated whether MMP-2 and -9 activities in the bile could be a marker for evaluation of liver metastasis in colorectal cancer. Fifty-three patients underwent colorectal resection for histologically verified adenocarcinoma. Twenty-six patients had colorectal cancer without liver metastasis and 27 patients had metastatic liver tumor. Six patients were studied as carcinoma-free control. MMP-2 and MMP-9 activities were assayed in bile using gelatin zymography and quantitated. Active MMP-2 activity of colorectal cancer with liver metastasis group (24.1 +/- 2.5 pixel count) was significantly higher than that of colorectal cancer without liver metastasis group (11.4 +/- 1.3 pixel count) (P < 0.001) or of control group (6.4 +/- 1.0 pixel count) (P < 0.001). Active MMP-9 was not detected in bile. ProMMP-9 activity of colorectal cancer with liver metastasis group (530.3 +/- 127.5 pixel count) was significantly higher than that of colorectal cancer without liver metastasis group (213.9 +/- 33.2 pixel count) (P = 0.008). This is the first report showing that the levels of active MMP-2 and proMMP-9 in bile were significantly higher in liver metastasis of colorectal cancer than in metastasis-free colorectal cancer. The results suggest that activities of active MMP-2 and proMMP-9 in the bile may be useful markers for predicting liver metastasis in colorectal cancer. 相似文献
87.
Makino K Yokoyama K Kubota Y Yutsudo CH Kimura S Kurokawa K Ishii K Hattori M Tatsuno I Abe H Iida T Yamamoto K Onishi M Hayashi T Yasunaga T Honda T Sasakawa C Shinagawa H 《Genes & genetic systems》1999,74(5):227-239
The enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain RIMD 0509952, derived from an outbreak in Sakai city, Japan, in 1996, produces two kinds of verotoxins, VT1 and VT2, encoded by the stx1 and stx2 genes. In the EHEC strains, as well as in other VT-producing E. coli strains, the toxins are encoded by lysogenic bacteriophages. The EHEC O157:H7 strain RIMD 0509952 did not produce plaque-forming phage particles upon inducing treatments. We have determined the complete nucleotide sequence of a prophage, VT2-Sakai, carrying the stx2A and stx2B genes on the chromosome, and presumed the putative functions of the encoded proteins and the cis-acting DNA elements based on sequence homology data. To our surprise, the sequences in the regions of VT2-Sakai corresponding to the early gene regulators and replication proteins, and the DNA sequences recognized by the regulators share very limited homology to those of the VT2-encoding 933W phage carried by the EHEC O157:H7 strain EDL933 reported by Plunkett et al. (J. Bacteriol., p1767-1778, 181, 1999), although the sequences corresponding to the structural components are almost identical. These data suggest that these two phages were derived from a common ancestral phage and that either or both of them underwent multiple genetic rearrangements. An IS629 insertion was found downstream of the stx2B gene and upstream of the lysis gene S, and this might be responsible for the absence of plaque-forming activity in the lysate obtained after inducing treatments. 相似文献
88.
Isshiki S Togayachi A Kudo T Nishihara S Watanabe M Kubota T Kitajima M Shiraishi N Sasaki K Andoh T Narimatsu H 《The Journal of biological chemistry》1999,274(18):12499-12507
89.
BIT (brain immunoglobulin-like molecule with tyrosine-based activation motifs) is a membrane glycoprotein that has two cytoplasmic TAMs (tyrosine-based activation motifs). We previously reported that tyrosine-phosphorylated TAMs of BIT interact with the Src homology 2 domain-containing protein tyrosine phosphatase SHP-2 both in vitro and in transfected cells, and this association results in a potent stimulation of the phosphatase activity of SHP-2. Both BIT and SHP-2 are highly expressed in the mammalian brain, and they may play important roles in the regulation of synaptic function. In this study, we found that nerve growth factor (NGF) treatment of PC12 cells leads to the tyrosine phosphorylation of BIT and a subsequent complex formation between BIT and SHP-2. Furthermore, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) also induced the tyrosine phosphorylation of BIT and the association with SHP-2 in primary cultured rat neurons. Our results suggest that the BIT-SHP-2 signaling pathway is a novel signal transduction mechanism of neurons that acts in response to neurotrophic factors such as NGF, BDNF, and NT-3. 相似文献
90.
The freezing behavior of xylem ray parenchyma cells in several boreal hardwood species, namely, Betula platyphylla, Populus canadensis, P. sieboldii, and Salix sachalinensis, was examined by differential thermal analysis (DTA), cryo-scanning electron microscopy (Cryo-SEM), and freeze-fracture replica electron microscopy. Although DTA profiles of samples harvested in summer and in winter suggested that the xylem ray parenchyma cells in all four species responded to freezing stress by extracellular freezing, Cryo-SEM showed clearly that the xylem ray parenchyma cells in all these species responded to freezing stress by shallow supercooling in summer and by extracellular freezing in winter. It is suggested that DTA failed to reveal the true freezing behavior of xylem ray parenchyma cells because of an overlap of temperature ranges between the high-temperature exotherm and the low-temperature exotherm and/or because of the limited extent of the LTE. The seasonal changes in freezing behavior of xylem ray parenchyma cells in all these boreal species, which are results of seasonal cold acclimation, support the hypothesis that a gradual shift of freezing behavior in xylem ray parenchyma cells from shallow supercooling in hardwood species that grow in tropical zones to extracellular freezing in hardwood species that grow in cold areas might be a result of the evolutionary adaptation of hardwood species to cold climates. Copyright 1999 Academic Press. 相似文献