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51.
Etsuko Kawashima Yasuhiro Nakanishi Yusuke Terui Hideyuki Tomitori Keiko Kashiwagi Yusuke Ohba 《Nucleosides, nucleotides & nucleic acids》2013,32(4):196-205
Pyrrole polyamide-2′-deoxyguanosine 5′-phosphate hybrid (Hybrid 4) was synthesized and evaluated in terms of the inhibition of mouse mammary carcinoma FM3A cell growth. Hybrid 4 was found to exhibit dose-dependent inhibition of cell growth. 相似文献
52.
Hiroshi Shiragami Yusuke Amino Yutaka Honda Masayuki Arai Yasuhiro Tanaka Hisao Iwagami 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):31-45
Abstract Practical method to produce 2′,3′-dideoxypurinenucleosides from 9-(2,5-di-O-acetyl-3-bromo-3-deoxy-β-D-xylofuranosyl)purines (1) was developed. High ratio of 2′,3′-dideoxynucleoside to 3′-deoxyribonucleoside was obtained by selecting the reaction conditions (solvent, pH and/or base), or changing 2′-acyloxy leaving group. The reaction mechanism was studied by deuteration experiments of 1a and 1-(3,5-di-O-acety1-2-bromo-2-deoxy-β-D-ribofuranosyl)thymine (12). 相似文献
53.
Yusuke Shiromoto Satomi Kuramochi-Miyagawa Akito Daiba Shinichiro Chuma Ami Katanaya Akiko Katsumata Ken Nishimura Manami Ohtaka Mahito Nakanishi Toshinobu Nakamura Koichi Yoshinaga Noriko Asada Shota Nakamura Teruo Yasunaga Kanako Kojima-Kita Daisuke Itou Tohru Kimura Toru Nakano 《RNA (New York, N.Y.)》2013,19(6):803-810
piRNA (PIWI-interacting RNA) is a germ cell–specific small RNA in which biogenesis PIWI (P-element wimpy testis) family proteins play crucial roles. MILI (mouse Piwi-like), one of the three mouse PIWI family members, is indispensable for piRNA production, DNA methylation of retrotransposons presumably through the piRNA, and spermatogenesis. The biogenesis of piRNA has been divided into primary and secondary processing pathways; in both of these MILI is involved in mice. To analyze the molecular function of MILI in piRNA biogenesis, we utilized germline stem (GS) cells, which are derived from testicular stem cells and possess a spermatogonial phenotype. We established MILI-null GS cell lines and their revertant, MILI-rescued GS cells, by introducing the Mili gene with Sendai virus vector. Comparison of wild-type, MILI-null, and MILI-rescued GS cells revealed that GS cells were quite useful for analyzing the molecular mechanisms of piRNA production, especially the primary processing pathway. We found that glycerol-3-phosphate acyltransferase 2 (GPAT2), a mitochondrial outer membrane protein for lysophosphatidic acid, bound to MILI using the cells and that gene knockdown of GPAT2 brought about impaired piRNA production in GS cells. GPAT2 is not only one of the MILI bound proteins but also a protein essential for primary piRNA biogenesis. 相似文献
54.
Daiki Miki Hidenori Ochi Atsushi Takahashi C. Nelson Hayes Yuji Urabe Hiromi Abe Tomokazu Kawaoka Masataka Tsuge Nobuhiko Hiraga Michio Imamura Yoshiiku Kawakami Hiroshi Aikata Shoichi Takahashi Norio Akuta Fumitaka Suzuki Kenji Ikeda Hiromitsu Kumada Yoshiyasu Karino Joji Toyota Tatsuhiko Tsunoda Michiaki Kubo Naoyuki Kamatani Yusuke Nakamura Kazuaki Chayama 《PloS one》2013,8(12)
Hepatitis C virus (HCV) establishes a chronic infection in 70-80% of infected individuals. Many researchers have examined the effect of human leukocyte antigen (HLA) on viral persistence because of its critical role in the immune response against exposure to HCV, but almost all studies have proven to be inconclusive. To identify genetic risk factors for chronic HCV infection, we analyzed 458,207 single nucleotide polymorphisms (SNPs) in 481 chronic HCV patients and 2,963 controls in a Japanese cohort. Next, we performed a replication study with an independent panel of 4,358 cases and 1,114 controls. We further confirmed the association in 1,379 cases and 25,817 controls. In the GWAS phase, we found 17 SNPs that showed suggestive association (P < 1 × 10-5). After the first replication study, we found one intronic SNP in the HLA-DQ locus associated with chronic HCV infection, and when we combined the two studies, the association reached the level of genome-wide significance. In the second replication study, we again confirmed the association (P
combined = 3.59 × 10−16, odds ratio [OR] = 0.79). Subsequent analysis revealed another SNP, rs1130380, with a stronger association (OR=0.72). This nucleotide substitution causes an amino acid substitution (R55P) in the HLA-DQB1 protein specific to the DQB1*03 allele, which is common worldwide. In addition, we confirmed an association with the previously reported IFNL3-IFNL4 locus and propose that the effect of DQB1*03 on HCV persistence might be affected by the IFNL4 polymorphism. Our findings suggest that a common amino acid substitution in HLA-DQB1 affects susceptibility to chronic infection with HCV in the Japanese population and may not be independent of the IFNL4 genotype. 相似文献
55.
Vincent Fraisier Amal Kasri Stéphanie Miserey-Lenkei Jean-Baptiste Sibarita Deepak Nair Adeline Mayeux Sabine Bardin Yusuke Toyoda Ina Poser Andrei Poznyakovskiy Bruno Goud Anthony A. Hyman Ariane Dimitrov 《PloS one》2013,8(12)
The Golgi apparatus is an intracellular compartment necessary for post-translational modification, sorting and transport of proteins. It plays a key role in mitotic entry through the Golgi mitotic checkpoint. In order to identify new proteins involved in the Golgi mitotic checkpoint, we combine the results of a knockdown screen for mitotic phenotypes and a localization screen. Using this approach, we identify a new Golgi protein C11ORF24 (NP_071733.1). We show that C11ORF24 has a signal peptide at the N-terminus and a transmembrane domain in the C-terminal region. C11ORF24 is localized on the Golgi apparatus and on the trans-Golgi network. A large part of the protein is present in the lumen of the Golgi apparatus whereas only a short tail extends into the cytosol. This cytosolic tail is well conserved in evolution. By FRAP experiments we show that the dynamics of C11ORF24 in the Golgi membrane are coherent with the presence of a transmembrane domain in the protein. C11ORF24 is not only present on the Golgi apparatus but also cycles to the plasma membrane via endosomes in a pH sensitive manner. Moreover, via video-microscopy studies we show that C11ORF24 is found on transport intermediates and is colocalized with the small GTPase RAB6, a GTPase involved in anterograde transport from the Golgi to the plasma membrane. Knocking down C11ORF24 does not lead to a mitotic phenotype or an intracellular transport defect in our hands. All together, these data suggest that C11ORF24 is present on the Golgi apparatus, transported to the plasma membrane and cycles back through the endosomes by way of RAB6 positive carriers. 相似文献
56.
PrPsc, the pathogenic isoform of PrPc, can convert PrPc into PrPsc through direct interactions. PrPc oligomerization is a required processing step before PrPsc formation, and soluble oligomers appear to be the toxic species in amyloid-related disorders. In the current study, direct interactions between vitamin D2 and human recombinant PrPc (90–231) were observed by Biacore assay, and 3F4 antibody, specific for amino acid fragment 109–112 of PrPc, inhibited this interaction. An ELISA study using3F4 antibody showed that PrPc (101–130), corresponding sequence to human PrP, was affected by vitamin D2, supporting the results of Biacore studies and suggesting that the PrPc sequence around the 3F4 epitope was responsible for the interaction with vitamin D2. Furthermore, the effects of vitamin D2 on disruption of PrPc (90–231) oligomerization were elucidated by dot blot analysis and differential protease k susceptibilities. While many chemical compounds have been proposed as potential therapeutic agents for the treatment of scrapie, most of these are toxic. However, given the safety and blood brain barrier permeability of vitamin D2, we propose that vitamin D2 may be a suitable agent to target PrPc in the brain and therefore is a potential therapeutic candidate for prion disease. 相似文献
57.
Shutaro Ishimura Masato Furuhashi Yuki Watanabe Kyoko Hoshina Takahiro Fuseya Tomohiro Mita Yusuke Okazaki Masayuki Koyama Marenao Tanaka Hiroshi Akasaka Hirofumi Ohnishi Hideaki Yoshida Shigeyuki Saitoh Tetsuji Miura 《PloS one》2013,8(11)
Objective
Fatty acid-binding proteins (FABPs) are a family of 14-15-kDa proteins, and some FABPs have been to be used as biomarkers of tissue injury by leak from cells. However, recent studies have shown that FABPs can be secreted from cells into circulation. Here we examined determinants and roles of circulating FABPs in a general population.Methods
From the database of the Tanno-Sobetsu Study, a study with a population-based cohort design, data in 2011 for 296 subjects on no medication were retrieved, and FABP1∼5 in their serum samples were assayed.Results
Level of FABP4, but not the other isoforms, showed a gender difference, being higher in females than in males. Levels of all FABPs were negatively correlated with estimated glomerular filtration rate (eGFR), but a distinct pattern of correlation with other clinical parameters was observed for each FABP isoform; significant correlates were alanine aminotransferase (ALT), blood pressure (BP), and brain natriuretic peptide (BNP) for FABP1, none besides eGFR for FABP2, age, BP, and BNP for FABP3, age, waist circumference (WC), BP, BNP, lipid variables, high-sensitivity C-reactive protein (hsCRP), and HOMA-R for FABP4, and age, WC, BP, ALT, BNP, and HOMA-R for FABP5. FABP4 is the most strongly related to metabolic markers among FABPs. In a multivariate regression analysis, FABP4 level was an independent predictor of HOMA-R after adjustment of age, gender, WC, BP, HDL cholesterol, and hsCRP.Conclusions
Each FABP isoform level showed a distinct pattern of correlation with clinical parameters, although levels of all FABPs were negatively determined by renal function. Circulating FABP4 appears to be a useful biomarker for detecting pre-clinical stage of metabolic syndrome, especially insulin resistance, in the general population. 相似文献58.
59.
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
60.
Notch signaling is an evolutionarily conserved signaling pathway and is essential for cell-fate specification in metazoans. Dysregulation of Notch signaling results in various human diseases, including cardiovascular defects and cancer. In 2000, Fringe, a known regulator of Notch signaling, was discovered as a Notch-modifying glycosyltransferase. Since then, glycosylation—a post-translational modification involving literal sugars—on the Notch extracellular domain has been noted as a critical mechanism for the regulation of Notch signaling. Additionally, the presence of diverse O-glycans decorating Notch receptors has been revealed in the extracellular domain epidermal growth factor-like (EGF) repeats. Here, we concisely summarize the recent studies in the human diseases associated with aberrant Notch glycosylation. 相似文献