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51.
Hiroaki Ozaki Yuichi Sato Sadaji Azuma Hiroaki Sawai 《Nucleosides, nucleotides & nucleic acids》2013,32(3):593-601
Abstract 2′-Deoxy-2′-S-hexyluridine derivative was synthesized from 2,2′-anhydrouridine and 1-hexanethiol and incorporated into an oligodeoxyribonucleotide. The thermal stability of the duplexes formed by the 2′-S-hexyl modified ODN with either the complementary DNA or RNA strand was decreased compared to the unmodified counterparts. 相似文献
52.
Brian A. Otter Shirish A. Patil Marianne R. Spada Linda A. Jelicks Yuichi Yoshimura Akira Matsuda 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):615-635
Abstract The 5-oxo-6-methylene-pyrimidine-2,4-dione intermediate (6) that is formed when 5-acetoxy-6-acetoxymethyl-1-β-D-(5-O-acetyl-2,3-O-isopropylidene)-ribofuranosyluracil (5) is treated with sodium hydroxide undergoes cyclization at pH 14 to give 2′,3′-O-isopropylidene-5-hydroxy- O 5, 6-methanouridine (8) in good yield. Conversion of 8 into the 5-triflate ester 14 followed by reduction with [(Ph)3P]4Pd/Bu3SnH and deblocking with acetic acid then affords O 5′, 6-methanouridine (4) Conformational studies (NOE difference spectra, vicinal 1H-13C coupling constants, NOESY and CD spectra, molecular modeling) indicate that the C7-methylene group of 4 projects towards the furanose ring oxygen atom, producing a glycosyl rotation angle of about ? 160°. 相似文献
53.
Siriporn Pota Sinchai Chatasiri Yoshitaka Ono Yuichi Yamaoka Makoto Kakishima 《Mycoscience》2013,54(1):19-28
Phakopsora meliosmae, a macrocyclic autoecious rust fungus, is reported to occur on several Meliosma species widely distributed in Asia. Despite the apparent broad host range, a recent molecular phylogenetic study indicated that two rust populations on Meliosma myriantha and Meliosma tenuis respectively in Japan were biologically distinct. To clarify the biological and taxonomic relationships of these populations, cross inoculations and comparative morphological examinations were carried out. Cross inoculations using basidiospores and aeciospores confirmed the macrocyclic, autoecious nature of the life cycle in both rust populations and showed that the two populations were distinct in their host specificity. Furthermore, they were found to be distinct in the structure of the aecial peridium surface, the size and wall thickness of uredinial paraphyses, and the urediniospore size and shape. Consequently, the fungal population on M. tenuis is taxonomically separated from P. meliosmae originally proposed for the fungus on M. myriantha. A new name, Phakopsora orientalis, is proposed for the fungus on M. tenuis. 相似文献
54.
Nami Masubuchi Yuichi Shidoh Shunzo Kondo Jun Takatoh Kazunori Hanaoka 《Experimental Animals》2013,62(3):211-217
Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive muscle
degenerative disorder that causes dilated cardiomyopathy in the second decade of life in
affected males. Dystrophin, the gene responsible for DMD, encodes
full-length dystrophin and various short dystrophin isoforms. In the mouse heart,
full-length dystrophin Dp427 and a short dystrophin isoform, Dp71, are expressed. In this
study, we intended to clarify the functions of these dystrophin isoforms in DMD-related
cardiomyopathy. We used two strains of mice: mdx mice, in which Dp427 was
absent but Dp71 was present, and DMD-null mice, in which both were
absent. By immunohistochemical staining and density-gradient centrifugation, we found that
Dp427 was located in the cardiac sarcolemma and also at the T-tubules, whereas Dp71 was
specifically located at the T-tubules. In order to determine whether T tubule-associated
Dp71 was involved in DMD-related cardiac disruption, we compared the cardiac phenotypes
between DMD-null mice and mdx mice. Both
DMD-null mice and mdx mice exhibited severe necrosis,
which was followed by fibrosis in cardiac muscle. However, we could not detect a
significant difference in myocardial fibrosis between mdx mice and
DMD-null mice. Based on the present results, we have shown that cardiac
myopathy is caused predominantly by a deficiency of full-length dystrophin Dp427. 相似文献
55.
Native vegetation is frequently replaced by alien plants on isolated oceanic islands. The effects of such replacements by invasive plants on the diversity and temporal dynamics of island-endemic insects remain unclear. We examined flying insect communities using Malaise traps on the small island of Nishi-jima in the oceanic Ogasawara Archipelago in the northwestern Pacific. On the island, an alien tree, Casuarina equisetifolia, has become dominant, occupying 57.3?% of the vegetation area. The species richness, composition, and abundance of pollinators (bees), predators (wasps), and wood-boring beetles (cerambycids, mordellids, and elaterids) were compared in each summer season of 4?years among three vegetation types: C. equisetifolia forest, natural forest, and grassland. In the traps, 82.3?% of species captured were endemic to the archipelago. The grassland harbored the highest species richness of native bees and wasps, whereas the natural forest had the highest species richness of native wood-boring beetles. The C. equisetifolia forest had the poorest species richness for most insect groups. Principal response curves indicated that differences in species composition among the three vegetation types were consistent through time for all insect groups. Most insect species were more abundant in natural forest or grassland than in C. equisetifolia forest. Standard deviations in both the numbers of individuals and species estimated under a Bayesian framework suggested that annual fluctuations of abundance and species density were similar among vegetation types (except for elaterid abundance). Therefore, replacement by C. equisetifolia has likely altered insect species composition but has not necessarily dramatically affected the temporal dynamics of insect assemblages on the island. 相似文献
56.
Teppei Yamada Koichi Azuma Emi Muta Jintaek Kim Shunichi Sugawara Guang Lan Zhang Satoko Matsueda Yuri Kasama-Kawaguchi Yuichi Yamashita Takuto Yamashita Kazuto Nishio Kyogo Itoh Tomoaki Hoshino Tetsuro Sasada 《PloS one》2013,8(11)
Treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, has achieved high clinical response rates in patients with non–small cell lung cancers (NSCLCs). However, over time, most tumors develop acquired resistance to EGFR-TKIs, which is associated with the secondary EGFR T790M resistance mutation in about half the cases. Currently there are no effective treatment options for patients with this resistance mutation. Here we identified two novel HLA-A*0201 (A2)-restricted T cell epitopes containing the mutated methionine residue of the EGFR T790M mutation, T790M-5 (MQLMPFGCLL) and T790M-7 (LIMQLMPFGCL), as potential targets for EGFR-TKI-resistant patients. When peripheral blood cells were repeatedly stimulated in vitro with these two peptides and assessed by antigen-specific IFN-γ secretion, T cell lines responsive to T790M-5 and T790M-7 were established in 5 of 6 (83%) and 3 of 6 (50%) healthy donors, respectively. Additionally, the T790M-5- and T790M-7-specific T cell lines displayed an MHC class I-restricted reactivity against NSCLC cell lines expressing both HLA-A2 and the T790M mutation. Interestingly, the NSCLC patients with antigen-specific T cell responses to these epitopes showed a significantly less frequency of EGFR-T790M mutation than those without them [1 of 7 (14%) vs 9 of 15 (60%); chi-squared test, p = 0.0449], indicating the negative correlation between the immune responses to the EGFR-T790M-derived epitopes and the presence of EGFR-T790M mutation in NSCLC patients. This finding could possibly be explained by the hypothesis that immune responses to the mutated neo-antigens derived from T790M might prevent the emergence of tumor cell variants with the T790M resistance mutation in NSCLC patients during EGFR-TKI treatment. Together, our results suggest that the identified T cell epitopes might provide a novel immunotherapeutic approach for prevention and/or treatment of EGFR-TKI resistance with the secondary EGFR T790M resistance mutation in NSCLC patients. 相似文献
57.
Yuichi Nozawa Takeji Umemura Satoru Joshita Yoshihiko Katsuyama Soichiro Shibata Takefumi Kimura Susumu Morita Michiharu Komatsu Akihiro Matsumoto Eiji Tanaka Masao Ota 《PloS one》2013,8(12)
Natural killer cell responses play a crucial role in virus clearance by the innate immune system. Although the killer immunoglobulin-like receptor (KIR) in combination with its cognate human leukocyte antigen (HLA) ligand, especially KIR2DL3-HLA-C1, is associated with both treatment-induced and spontaneous clearance of hepatitis C virus (HCV) infection in Caucasians, these innate immunity genes have not been fully clarified in Japanese patients. We therefore investigated 16 KIR genotypes along with HLA-B and -C ligands and a genetic variant of interleukin (IL) 28B (rs8099917) in 115 chronic hepatitis C genotype 1 patients who underwent pegylated-interferon-α2b (PEG-IFN) and ribavirin therapy. HLA-Bw4 was significantly associated with a sustained virological response (SVR) to treatment (P = 0.017; odds ratio [OR] = 2.50, ), as was the centromeric A/A haplotype of KIR (P = 0.015; OR 3.37). In contrast, SVR rates were significantly decreased in patients with KIR2DL2 or KIR2DS2 (P = 0.015; OR = 0.30, and P = 0.025; OR = 0.32, respectively). Multivariate logistic regression analysis subsequently identified the IL28B TT genotype (P = 0.00009; OR = 6.87, 95% confidence interval [CI] = 2.62 - 18.01), KIR2DL2/HLA-C1 (P = 0.014; OR = 0.24, 95% CI = 0.08 - 0.75), KIR3DL1/HLA-Bw4 (P = 0.008, OR = 3.32, 95% CI = 1.37 - 8.05), and white blood cell count at baseline (P = 0.009; OR = 3.32, 95% CI = 1.35 - 8.16) as independent predictive factors of an SVR. We observed a significant association between the combination of IL28B TT genotype and KIR3DL1-HLA-Bw4 in responders (P = 0.0019), whereas IL28B TT along with KIR2DL2-HLA-C1 was related to a non-response (P = 0.0067). In conclusion, combinations of KIR3DL1/HLA-Bw4, KIR2DL2/HLA-C1, and a genetic variant of the IL28B gene are predictive of the response to PEG-IFN and ribavirin therapy in Japanese patients infected with genotype 1b HCV. 相似文献
58.
59.
Aniruddha Chatterjee Yuichi Ozaki Peter A Stockwell Julia A Horsfield Ian M Morison Shinichi Nakagawa 《Epigenetics》2013,8(9):979-989
Reduced representation bisulfite sequencing (RRBS) has been used to profile DNA methylation patterns in mammalian genomes such as human, mouse and rat. The methylome of the zebrafish, an important animal model, has not yet been characterized at base-pair resolution using RRBS. Therefore, we evaluated the technique of RRBS in this model organism by generating four single-nucleotide resolution DNA methylomes of adult zebrafish brain. We performed several simulations to show the distribution of fragments and enrichment of CpGs in different in silico reduced representation genomes of zebrafish. Four RRBS brain libraries generated 98 million sequenced reads and had higher frequencies of multiple mapping than equivalent human RRBS libraries. The zebrafish methylome indicates there is higher global DNA methylation in the zebrafish genome compared with its equivalent human methylome. This observation was confirmed by RRBS of zebrafish liver. High coverage CpG dinucleotides are enriched in CpG island shores more than in the CpG island core. We found that 45% of the mapped CpGs reside in gene bodies, and 7% in gene promoters. This analysis provides a roadmap for generating reproducible base-pair level methylomes for zebrafish using RRBS and our results provide the first evidence that RRBS is a suitable technique for global methylation analysis in zebrafish. 相似文献
60.
Caiyong Chen Daniel Garcia-Santos Yuichi Ishikawa Alexandra Seguin Liangtao Li Katherine H. Fegan Gordon J. Hildick-Smith Dhvanit I. Shah Jeffrey D. Cooney Wen Chen Matthew J. King Yvette Y. Yien Iman J. Schultz Heidi Anderson Arthur J. Dalton Matthew L. Freedman Paul D. Kingsley James Palis Barry H. Paw 《Cell metabolism》2013,17(3):343-352
Highlights? Snx3 is highly expressed in vertebrate hematopoietic tissues ? Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates ? Snx3 and Vps35 physically interact with Tfrc ? Snx3 is required for endosomal recycling of Tf-Tfrc complex 相似文献