全文获取类型
收费全文 | 1393篇 |
免费 | 102篇 |
专业分类
1495篇 |
出版年
2023年 | 3篇 |
2022年 | 19篇 |
2021年 | 30篇 |
2020年 | 19篇 |
2019年 | 17篇 |
2018年 | 40篇 |
2017年 | 44篇 |
2016年 | 45篇 |
2015年 | 60篇 |
2014年 | 69篇 |
2013年 | 199篇 |
2012年 | 91篇 |
2011年 | 98篇 |
2010年 | 65篇 |
2009年 | 50篇 |
2008年 | 94篇 |
2007年 | 84篇 |
2006年 | 62篇 |
2005年 | 55篇 |
2004年 | 81篇 |
2003年 | 60篇 |
2002年 | 61篇 |
2001年 | 10篇 |
2000年 | 8篇 |
1999年 | 11篇 |
1998年 | 16篇 |
1997年 | 7篇 |
1996年 | 18篇 |
1995年 | 13篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1982年 | 4篇 |
1980年 | 2篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1909年 | 2篇 |
1907年 | 2篇 |
1906年 | 2篇 |
1905年 | 2篇 |
1904年 | 2篇 |
排序方式: 共有1495条查询结果,搜索用时 0 毫秒
61.
Maria V. Croce Marcela Fejes Norma Riera D. A. Minoldo Amada Segal-Eiras 《Cancer immunology, immunotherapy : CII》1985,20(1):91-95
Summary A total of 122 sera from acute lymphoblastic leukemia (ALL) patients were analyzed for circulating immune complexes (CIC) by two methods: the 125I-C1q binding assay and the polyethylene glycol precipitation test (PEG). The results were correlated with induction, remission and relapse stages of the disease. Using the first method the levels of CIC in induction were 15.18±9.15, with 19/29 positive cases (65.50%), P<0.001 compared with controls. In the remission phase the levels were 9.02±5.62, 11/45 (24.49%) nonsignificant P value, and in relapse they were 16.14±11.17 28/48 (58.33%) P<0.001. The PEG precipitation test results were: 0.33±0.10, 8/22 (36.36%); 0.24±0.11, 10/48 (20.83%) and 0.28±0.10, 6/28 (21.42%), respectively. Thus the values of CIC as measured by PEG in the three clinical of phases ALL did not differ significantly from controls. This contrasts with results obtained by the radioiodinated C1q binding assay, where the incidence of positive values was significantly higher in induction and in relapse and lower in the remission phase. These observations were extended in sequential vertical studies performed in a group of patients. These results suggest that raised CIC detected by the 125I-C1q method may reflect a progressive state in ALL and that quantitation of these immune complexes may provide an adequate biochemical marker for prognosis. 相似文献
62.
Involvement of herpes simplex virus type 1 UL13 protein kinase in induction of SOCS genes,the negative regulators of cytokine signaling 下载免费PDF全文
63.
Astrocytes with previous chronic exposure to amyloid β‐peptide fragment 1–40 suppress excitatory synaptic transmission 下载免费PDF全文
Hiroyuki Kawano Kohei Oyabu Hideaki Yamamoto Kei Eto Yuna Adaniya Kaori Kubota Takuya Watanabe Ayumi Hirano‐Iwata Junichi Nabekura Shutaro Katsurabayashi Katsunori Iwasaki 《Journal of neurochemistry》2017,143(6):624-634
64.
Mammalian Genome - While CpG dinucleotides are significantly reduced compared to other dinucleotides in mammalian genomes, they can congregate and form CpG islands, which localize around... 相似文献
65.
Sayuki Iijima Kentaro Matsuura Tsunamasa Watanabe Koji Onomoto Takashi Fujita Kyoko Ito Etsuko Iio Tomokatsu Miyaki Kei Fujiwara Noboru Shinkai Atsunori Kusakabe Mio Endo Shunsuke Nojiri Takashi Joh Yasuhito Tanaka 《PloS one》2015,10(2)
The levels of expression of interferon-stimulated genes (ISGs) in liver are associated with response to treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV). However, associations between the responses of ISGs to IFN-based therapy and treatment efficacy or interleukin-28B (IL28B) genotype have not yet been determined. Therefore, we investigated the early responses of ISGs and interferon-lambdas (IFN-λs) in peripheral blood mononuclear cells (PBMCs) during PEG-IFN/RBV plus NS3/4 protease inhibitor (PI) therapy. We prospectively enrolled 50 chronic hepatitis C patients with HCV genotype 1, and collected PBMCs at baseline, 8 and 24 h after the initial administration of PEG-IFN/RBV/PI. Levels of mRNAs for selected ISGs and IFN-λs were evaluated by real-time PCR. All 31 patients with a favorable IL28B genotype and 13 of 19 with an unfavorable genotype achieved sustained virological responses (SVR). Levels of mRNA for A20, SOCS1, and SOCS3, known to suppress antiviral activity by interfering with the IFN signaling pathway, as well as IRF1 were significantly higher at 8 h in patients with an unfavorable IL28B genotype than in those with a favorable one (P = 0.007, 0.026, 0.0004, 0.0006, respectively), especially in the non-SVR group. Particularly, the fold-change of IRF1 at 8 h relative to baseline was significantly higher in non-SVR than in SVR cases with an unfavorable IL28B genotype (P = 0.035). In conclusion, levels of several mRNAs of genes suppressing antiviral activity in PBMCs during PEG-IFN/RBV/PI differed according to IL28B genotypes, paralleling treatment efficacy. 相似文献
66.
Common Neutralization Epitope in Minor Capsid Protein L2 of Human Papillomavirus Types 16 and 6 总被引:6,自引:0,他引:6 下载免费PDF全文
Kei Kawana Hiroyuki Yoshikawa Yuji Taketani Kunito Yoshiike Tadahito Kanda 《Journal of virology》1999,73(7):6188-6190
Studies of virus neutralization by antibody are a prerequisite for development of a prophylactic vaccine strategy against human papillomaviruses (HPVs). Using HPV16 and -6 pseudovirions capable of inducing beta-galactosidase in infected monkey COS-1 cells, we examined the neutralizing activity of mouse monoclonal antibodies (MAbs) that recognize surface epitopes in HPV16 minor capsid protein L2. Two MAbs binding to a synthetic peptide with the HPV16 L2 sequence of amino acids (aa) 108 to 120 were found to inhibit pseudoinfections with HPV16 as well as HPV6. Antisera raised by immunizing BALB/c mice with the synthetic peptide had a cross-neutralizing activity similar to that of the MAb. The data indicate that HPV16 and -6 have a common cross-neutralization epitope (located within aa 108 to 120 of L2 in HPV16), suggesting that this epitope may be shared by other genital HPVs. 相似文献
67.
Nakano M Ikeda Y Tokuda Y Fuwa M Omi N Ueno M Imai K Adachi H Kageyama M Mori K Kinoshita S Tashiro K 《PloS one》2012,7(3):e33389
Background
To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated.Methods and Principal Findings
We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10−10). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients.Conclusions and Significance
In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma. 相似文献68.
Maki Kiso Kyoko Shinya Masayuki Shimojima Ryo Takano Kei Takahashi Hiroaki Katsura Satoshi Kakugawa Mai thi Quynh Le Makoto Yamashita Yousuke Furuta Makoto Ozawa Yoshihiro Kawaoka 《PLoS pathogens》2010,6(8)
Influenza viruses resistant to antiviral drugs emerge frequently. Not surprisingly, the widespread treatment in many countries of patients infected with 2009 pandemic influenza A (H1N1) viruses with the neuraminidase (NA) inhibitors oseltamivir and zanamivir has led to the emergence of pandemic strains resistant to these drugs. Sporadic cases of pandemic influenza have been associated with mutant viruses possessing a histidine-to-tyrosine substitution at position 274 (H274Y) in the NA, a mutation known to be responsible for oseltamivir resistance. Here, we characterized in vitro and in vivo properties of two pairs of oseltaimivir-sensitive and -resistant (possessing the NA H274Y substitution) 2009 H1N1 pandemic viruses isolated in different parts of the world. An in vitro NA inhibition assay confirmed that the NA H274Y substitution confers oseltamivir resistance to 2009 H1N1 pandemic viruses. In mouse lungs, we found no significant difference in replication between oseltamivir-sensitive and -resistant viruses. In the lungs of mice treated with oseltamivir or even zanamivir, 2009 H1N1 pandemic viruses with the NA H274Y substitution replicated efficiently. Pathological analysis revealed that the pathogenicities of the oseltamivir-resistant viruses were comparable to those of their oseltamivir-sensitive counterparts in ferrets. Further, the oseltamivir-resistant viruses transmitted between ferrets as efficiently as their oseltamivir-sensitive counterparts. Collectively, these data indicate that oseltamivir-resistant 2009 H1N1 pandemic viruses with the NA H274Y substitution were comparable to their oseltamivir-sensitive counterparts in their pathogenicity and transmissibility in animal models. Our findings highlight the possibility that NA H274Y-possessing oseltamivir-resistant 2009 H1N1 pandemic viruses could supersede oseltamivir-sensitive viruses, as occurred with seasonal H1N1 viruses. 相似文献
69.
Recent studies have shown a dampened amplitude of clock gene rhythm in the heart and liver of streptozotocin (STZ)-treated rats and mice, however it is unknown whether impairment is due to dysfunction of the suprachiasmatic nucleus (SCN) or not. Rhythmic expression of mPER2 was dampened in the STZ-treated mouse liver but not SCN and cerebral cortex. Injection of insulin could normalize an impairment of mPer2 and mPER2 expression rhythm in the liver, when it was injected at nighttime, but not at daytime. In the present study, we demonstrated that insulin-dependent diabetes impaired oscillation of the peripheral clock gene and its product. Insulin injection can recover dampened oscillation of the peripheral clock depending on its injection time. 相似文献