全文获取类型
收费全文 | 1190篇 |
免费 | 57篇 |
出版年
2022年 | 2篇 |
2021年 | 8篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 12篇 |
2017年 | 14篇 |
2016年 | 23篇 |
2015年 | 27篇 |
2014年 | 40篇 |
2013年 | 85篇 |
2012年 | 65篇 |
2011年 | 67篇 |
2010年 | 49篇 |
2009年 | 49篇 |
2008年 | 67篇 |
2007年 | 70篇 |
2006年 | 53篇 |
2005年 | 82篇 |
2004年 | 82篇 |
2003年 | 85篇 |
2002年 | 78篇 |
2001年 | 12篇 |
2000年 | 12篇 |
1999年 | 19篇 |
1998年 | 19篇 |
1997年 | 17篇 |
1996年 | 15篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 11篇 |
1992年 | 14篇 |
1991年 | 15篇 |
1990年 | 18篇 |
1989年 | 11篇 |
1988年 | 13篇 |
1987年 | 11篇 |
1986年 | 4篇 |
1985年 | 8篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 5篇 |
1973年 | 8篇 |
1972年 | 3篇 |
排序方式: 共有1247条查询结果,搜索用时 46 毫秒
31.
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
32.
Mari Narusaka Yasuyuki Kubo Katsunori Hatakeyama Jun Imamura Hiroshi Ezura Yoshihiko Nanasato Yutaka Tabei Yoshitaka Takano Ken Shirasu Yoshihiro Narusaka 《PloS one》2013,8(2)
A major class of disease resistance (R) genes which encode nucleotide binding and leucine rich repeat (NB-LRR) proteins have been used in traditional breeding programs for crop protection. However, it has been difficult to functionally transfer NB-LRR-type R genes in taxonomically distinct families. Here we demonstrate that a pair of Arabidopsis (Brassicaceae) NB-LRR-type R genes, RPS4 and RRS1, properly function in two other Brassicaceae, Brassica rapa and Brassica napus, but also in two Solanaceae, Nicotiana benthamiana and tomato (Solanum lycopersicum). The solanaceous plants transformed with RPS4/RRS1 confer bacterial effector-specific immunity responses. Furthermore, RPS4 and RRS1, which confer resistance to a fungal pathogen Colletotrichum higginsianum in Brassicaceae, also protect against Colletotrichum orbiculare in cucumber (Cucurbitaceae). Importantly, RPS4/RRS1 transgenic plants show no autoimmune phenotypes, indicating that the NB-LRR proteins are tightly regulated. The successful transfer of two R genes at the family level implies that the downstream components of R genes are highly conserved. The functional interfamily transfer of R genes can be a powerful strategy for providing resistance to a broad range of pathogens. 相似文献
33.
34.
Nungki Anggorowati Yoshihiko Yano Yanri Wijayanti Subronto Takako Utsumi Didik Setyo Heriyanto Deshinta Putri Mulya Hanggoro Tri Rinonce Dewiyani Indah Widasari Maria Inge Lusida Soetjipto Yoshitake Hayashi 《Microbiology and immunology》2013,57(4):298-308
GB virus C (GBV‐C), a human virus of the Flaviviridae family that is structurally and epidemiologically closest to hepatitis C virus (HCV), has been reported to confer beneficial outcomes in HIV‐positive patients. However, the prevalence of GBV‐C in HIV‐positive individuals in Indonesia is unknown. Since GBV‐C is more prevalent in anti‐HCV positive patients than in anti‐HCV negative subjects, transmission of GBV‐C and HCV could be by the same method. This study examined the prevalence and molecular characteristics of GBV‐C infection in HIV patients in Yogyakarta, Indonesia. The prevalence of GBV‐C among HIV patients (n = 125, median age 31 years) based on the 5′UTR region was 111/125 (88.8%), including 39/48 (81.3%) and 72/77 (93.5%) HIV‐infected patients with and without HCV infection, respectively. GBV‐C isolates were of genotype 2a, 3 and 6 in 58.3%, 12.6% and 28.4% of patients, respectively. Patients with genotype 3 were significantly younger than those with genotypes 2a or 6 (P = 0.001 and P = 0.012, respectively). Genotypes 3 and 6 were significantly associated with injection drug use (P = 0.004 and P = 0.002, respectively) and HCV co‐infection (P < 0.001 for both genotypes), indicating a shared transmission route with HCV. In conclusion, the prevalence of GBV‐C among HIV‐positive patients in Indonesia is high, and three genotypes were detected, namely genotype 2a, 3 and 6. 相似文献
35.
Keiji Nagaya Yoshihiko Matsui Hironobu Ohira Akira Yuasa Hiroyuki Yamamoto Kousaku Ohkawa 《Biofouling》2013,29(4):263-274
The attachment strength of the freshwater mussel Limnoperna fortunei against water flow was studied. Newton's expression successfully described the hydrodynamic drag force acting on the mussel with a drag coefficient value of 1.03. The drag‐resistant force (defined as hydrodynamic drag force at mussel detachment) was smaller than the detachment force measured using a tensile load test. A fairly good correlation was obtained between the drag‐resistant force and the number of secreted threads. The drag‐resistant force divided by the number of threads increased with shell size, suggesting that byssal thread strength increased with mussel growth. For the mussel specimens obtained from a water transmission pipe, thread width increased with shell size. However, thread width was not dependent on current velocity. There was no correlation between the number of secreted threads and shell length, which indicated that the number of secreted threads did not change with mussel size. Therefore, the water velocity needed to detach mussels increases with shell size of the mussel when the number of secreted threads is constant. The increases in the water velocity to detach mussels with larger shells suggests that the mussel becomes more resistant to water flow as it grows. It is estimated that a flow velocity of around lms‐1 is critical for attachment/detachment of a juvenile mussel with a shell length of a few millimeters and one hundred byssal threads. 相似文献
36.
Kousaku Ohkawa Ayako Nishida Reiko Honma Yoshihiko Matsui Keiji Nagaya Akira Yuasa 《Biofouling》2013,29(4):337-350
Attachment of the freshwater mussel, Limnoperna fortunei, was tested using non‐treated surfaces, viz. glass, nylon, rubber, silicone and Teflon, together with glass surfaces modified with nine kinds of silane coupling agents. Among the surfaces tested, the mussel avoided attaching to Teflon, silicone, and glass modified with 3‐bromopropyltrimethoxysilane or 3,3,3‐(trifluo‐ropropyl)‐trimethoxysilane. With respect to the relationship between the percentage attachment and the surface free energy (sfe) of the substrates, it was found that attachment was considerably reduced on the substrates which exhibited relatively low sfe, as above. The mean number of secreted byssuses per attaching mussel also decreased with decreasing substrate sfe. Furthermore, when the sfe was divided into the dispersion and polar components, the percentage mussel attachment was related to the polar component. These results suggest that effective antifouling towards L. fortunei is achieved on substrates with a low sfe polar component. 相似文献
37.
Tetsurou Muroi Takaaki Kokuzawa Yoshihiko Kihara Ryuichi Kobayashi Nobutaka Hirano Hideo Takahashi Mitsuru Haruki 《Applied microbiology and biotechnology》2013,97(9):4039-4048
Serine-type phage integrases catalyze unidirectional site-specific recombination between the attachment sites, attP and attB, in the phage and host bacterial genomes, respectively; these integrases and DNA target sites function efficiently when transferred into heterologous cells. We previously developed an in vivo site-specific genomic integration system based on actinophage TG1 integrase that introduces ~2-kbp DNA into an att site inserted into a heterologous Escherichia coli genome. Here, we analyzed the TG1 integrase-mediated integrations of att site-containing ~10-kbp DNA into the corresponding att site pre-inserted into various genomic locations; moreover, we developed a system that introduces ~10-kbp DNA into the genome with an efficiency of ~104 transformants/μg DNA. Integrations of attB-containing DNA into an attP-containing genome were more efficient than integrations of attP-containing DNA into an attB-containing genome, and integrations targeting attP inserted near the replication origin, oriC, and the E. coli “centromere” analogue, migS, were more efficient than those targeting attP within other regions of the genome. Because the genomic region proximal to the oriC and migS sites is located at the extreme poles of the cell during chromosomal segregation, the oriC–migS region may be more exposed to the cytosol than are other regions of the E. coli chromosome. Thus, accessibility of pre-inserted attP to attB-containing incoming DNA may be crucial for the integration efficiency by serine-type integrases in heterologous cells. These results may be beneficial to the development of serine-type integrases-based genomic integration systems for various bacterial species. 相似文献
38.
Takahiro Inoue Kyosuke Takao Takashi Yoshida Kei Wada Takashi Daifuku Yasuko Yoneda Keiichi Fukuyama Yoshihiko Sako 《Biochemical and biophysical research communications》2013
A unique [Ni–Fe–S] cluster (C-cluster) constitutes the active center of Ni-containing carbon monoxide dehydrogenases (CODHs). His261, which coordinates one of the Fe atoms with Cys295, is suggested to be the only residue required for Ni coordination in the C-cluster. To evaluate the role of Cys295, we constructed CODH-II variants. Ala substitution for the Cys295 substitution resulted in the decrease of Ni content and didn’t result in major change of Fe content. In addition, the substitution had no effect on the ability to assemble a full complement of [Fe–S] clusters. This strongly suggests Cys295 indirectly and His261 together affect Ni-coordination in the C-cluster. 相似文献
39.
Akiharu Kubo Aiko Shiohama Takashi Sasaki Kazuhiko Nakabayashi Hiroshi Kawasaki Toru Atsugi Showbu Sato Atsushi Shimizu Shuji Mikami Hideaki Tanizaki Masaki Uchiyama Tatsuo Maeda Taisuke Ito Jun-ichi Sakabe Toshio Heike Torayuki Okuyama Rika Kosaki Kenjiro Kosaki Jun Kudoh Kenichiro Hata Akihiro Umezawa Yoshiki Tokura Akira Ishiko Hironori Niizeki Kenji Kabashima Yoshihiko Mitsuhashi Masayuki Amagai 《American journal of human genetics》2013,93(5):945-956
“Nagashima-type” palmoplantar keratosis (NPPK) is an autosomal recessive nonsyndromic diffuse palmoplantar keratosis characterized by well-demarcated diffuse hyperkeratosis with redness, expanding on to the dorsal surfaces of the palms and feet and the Achilles tendon area. Hyperkeratosis in NPPK is mild and nonprogressive, differentiating NPPK clinically from Mal de Meleda. We performed whole-exome and/or Sanger sequencing analyses of 13 unrelated NPPK individuals and identified biallelic putative loss-of-function mutations in SERPINB7, which encodes a cytoplasmic member of the serine protease inhibitor superfamily. We identified a major causative mutation of c.796C>T (p.Arg266∗) as a founder mutation in Japanese and Chinese populations. SERPINB7 was specifically present in the cytoplasm of the stratum granulosum and the stratum corneum (SC) of the epidermis. All of the identified mutants are predicted to cause premature termination upstream of the reactive site, which inhibits the proteases, suggesting a complete loss of the protease inhibitory activity of SERPINB7 in NPPK skin. On exposure of NPPK lesional skin to water, we observed a whitish spongy change in the SC, suggesting enhanced water permeation into the SC due to overactivation of proteases and a resultant loss of integrity of the SC structure. These findings provide an important framework for developing pathogenesis-based therapies for NPPK. 相似文献
40.
Chisato Kusunoki Liu Yang Takeshi Yoshizaki Fumiyuki Nakagawa Atsushi Ishikado Motoyuki Kondo Katsutaro Morino Osamu Sekine Satoshi Ugi Yoshihiko Nishio Atsunori Kashiwagi Hiroshi Maegawa 《Biochemical and biophysical research communications》2013,430(1):225-230
Oxidative stress is produced in adipose tissue of obese subjects and has been associated with obesity-related disorders. Recent studies have shown that omega-3 polyunsaturated fatty acid (ω3-PUFA) has beneficial effects in preventing atherosclerotic diseases and insulin resistance in adipose tissue. However, the role of ω3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1 adipocytes were treated with ω3-PUFA and its metabolites, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). ω3-PUFA and its metabolites dose-dependently increased mRNA and protein levels of the anti-oxidative enzyme, heme oxygenase-1 (HO-1); whereas no changes in the well-known anti-oxidant molecules, superoxide dismutase, catalase, and glutathione peroxidase, were observed. Knockdown of nuclear factor erythroid 2-related factor 2 (Nrf-2) significantly reduced EPA, DHA or 4-HHE-induced HO-1 mRNA and protein expression. Also, pretreatment with ω3-PUFA prevented H2O2-induced cytotoxicity in a HO-1 dependent manner. In conclusion, treatment with EPA and DHA induced HO-1 through the activation of Nrf-2 and prevented oxidative stress in 3T3-L1 adipocytes. This anti-oxidant defense may be of high therapeutic value for clinical conditions associated with systemic oxidative stress. 相似文献