全文获取类型
收费全文 | 6033篇 |
免费 | 558篇 |
国内免费 | 3篇 |
出版年
2023年 | 15篇 |
2022年 | 63篇 |
2021年 | 99篇 |
2020年 | 83篇 |
2019年 | 111篇 |
2018年 | 171篇 |
2017年 | 143篇 |
2016年 | 224篇 |
2015年 | 306篇 |
2014年 | 386篇 |
2013年 | 398篇 |
2012年 | 580篇 |
2011年 | 471篇 |
2010年 | 339篇 |
2009年 | 291篇 |
2008年 | 407篇 |
2007年 | 403篇 |
2006年 | 377篇 |
2005年 | 291篇 |
2004年 | 285篇 |
2003年 | 262篇 |
2002年 | 176篇 |
2001年 | 104篇 |
2000年 | 87篇 |
1999年 | 63篇 |
1998年 | 45篇 |
1997年 | 35篇 |
1996年 | 24篇 |
1995年 | 23篇 |
1994年 | 25篇 |
1993年 | 9篇 |
1992年 | 30篇 |
1991年 | 23篇 |
1990年 | 25篇 |
1989年 | 19篇 |
1988年 | 25篇 |
1987年 | 16篇 |
1986年 | 17篇 |
1985年 | 14篇 |
1984年 | 13篇 |
1983年 | 12篇 |
1982年 | 11篇 |
1981年 | 15篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1976年 | 5篇 |
1975年 | 5篇 |
1973年 | 6篇 |
1972年 | 8篇 |
排序方式: 共有6594条查询结果,搜索用时 15 毫秒
951.
Changsoo Lee Min Jeong JongAh Joanne Lee Saebom Seo Sung Chun Cho Wei Zhang 《MABS-AUSTIN》2017,9(6):968-977
As biosimilars enter the market, comparisons of product quality are needed. Manufacturing differences may lead to differences in critical quality attributes, which affect efficacy. Therefore, critical quality attributes (structure and biological activity) of Remicade® and of 2 biosimilar products (Flixabi®/Renflexis® and Remsima®/Inflectra®) were determined. We assessed binding to tumor necrosis factor in a fluorescence competitive binding assay; potency in a luciferase reporter gene assay; percentages of galactosylated glycan, afucose plus high mannosylated glycans, and charged glycan; FcγRIIIa (CD16) binding (assessed by 3 methods); and antibody-dependent cell-mediated cytotoxicity (ADCC) in the NK92-CD16a cell line and in peripheral blood mononuclear cells (PBMC). The results of Fab-related activity were similar for all products. Compared with Remicade®, Flixabi® had a lower percentage of charged glycan, and Remsima® had a higher percentage of galactosylated glycan and a lower percentage of afucose plus high mannosylated glycans. Whereas Remsima® and Remicade® are expressed in a Sp2/0 cell line, Flixabi® is expressed in a CHO cell line. Despite this difference, galactosylated glycans from the 3 products were not correlated with the expression system. The results of all 3 methods used in this study indicated that FcγRIIIa binding was lower with Remsima® than with Remicade®. The percentage of ADCC in NK92-CD16a cells was lower with Remsima® and higher with Flixabi® compared with Remicade®, but was similar for all 3 products in PBMC. Surface expression of CD16 was 5.7-fold greater on NK92-CD16a cells than on PBMC. Combined percentages of afucosylated and high mannosylated glycans were positively correlated with FcγRIIIa binding and ADCC in NK92-CD16 cells, while no correlation was observed in PBMC. 相似文献
952.
A viable option for increasing nitrogen (N) use efficiency and mitigation of negative impacts of N on the environment is to capitalize on multi-element interactions through implementation of nutrient management programs that provide balanced nutrition. Numerous studies have demonstrated the immediate efficacy of this approach in the developing regions like China and India as well as developed countries in North America. Based on 241 site-years of experiments in these countries, the first-year N recovery efficiency (RE) for the conventional or check treatments averaged 21% while the balanced treatments averaged 54% RE, for an average increase of 33% in RE due to balanced nutrition. Effective policies to promote adoption are most likely those that enable site-specific approaches to nutrient management decisions rather than sweeping, nation-wide incentives supporting one nutrient over another. Local farmers, advisers and officials need to be empowered with tools and information to help them define necessary changes in practices to create more balanced nutrient management. 相似文献
953.
Eunkyung Kim Ji‐Yun Hwang Eun‐Kyung Woo Sung‐Soo Kim Sangmee Ahn Jo Inho Jo 《Obesity (Silver Spring, Md.)》2005,13(9):1510-1514
Objectives: To establish BMI percentiles and cutoffs for underweight, overweight, and obesity in South Korean schoolgirls. Research Methods and Procedures: A total of 1229 South Korean schoolgirls aged 8 to 18 years were randomly selected to complete a self‐administered questionnaire. BMI charts and cutoffs were constructed after analyzing data from 1107 subjects. Percentile curves were established by the modified LMS method. Results: The percentiles for underweight, overweight, and obesity corresponding to BMI of 18.5, 23.0, and 25.0 kg/m2 at age 18 were the 13.0th percentile, the 77.8th percentile, and the 91.2nd percentile, respectively. The corresponding prevalences of underweight, overweight, and obesity were 12.1, 12.5, and 9.8%, respectively. Discussion: We established for the first time, to our knowledge, new BMI cutoffs for ages 8 to 18 that corresponded to BMIs of 18.5, 23.0, and 25.0 kg/m2 for Asian adults designated by the International Obesity Task Force. These newly established BMI cutoffs might help to estimate the prevalence of overweight and obesity in Asian children. 相似文献
954.
Biological systems in nano-scale, due to the weak electrostatic interactions and structural connectivity therein, are flexible
so that they undergo conformational transition subject to thermal fluctuations and external noises. In the presence of barriers,
nature utilizes the fluctuations to give rise to self-organization, typically accompanied by conformational transitions. In
two opposing membranes with like-charges, the cooperative coupling between the undulation and charge fluctuations give rise
to a dynamic instability to spontaneous growth of the in-phase membrane undulation, and thus a great reduction of the energy
barrier to fusion. The multivalent counter-ions, the Ca2+ for example, enhance the necessary charge density fluctuation leading to surface charge inversion and overcondensation. 相似文献
955.
A series of new expression vectors (pPro) have been constructed for the regulated expression of genes in Escherichia coli. The pPro vectors contain the prpBCDE promoter (PprpB) responsible for expression of the propionate catabolic genes (prpBCDE) and prpR encoding the positive regulator of this promoter. The efficiency and regulatory properties of the prpR-PprpB system were measured by placing the gene encoding the green fluorescent protein (gfp) under the control of the inducible PprpB of E. coli. This system provides homogenous expression in individual cells, highly regulatable expression over a wide range of propionate concentrations, and strong expression (maximal 1,500-fold induction) at high propionate concentrations. Since the prpBCDE promoter has CAP-dependent activation, the prpR-PprpB system exhibited negligible basal expression by addition of glucose to the medium. 相似文献
956.
Introduction of tyramide signal amplification (TSA) to pre-embedding nanogold-silver staining at the electron microscopic level. 总被引:3,自引:0,他引:3
Seung-won Lee Song Eun Lee Seong Hyuk Ko Eun Kyoung Hong Kwang Il Nam Kei-ichiro Nakamura Shuhei Imayama Yeong-Joon Park Kyu Youn Ahn Choon Sang Bae Baik Yoon Kim Sung Sik Park 《The journal of histochemistry and cytochemistry》2005,53(2):249-252
The tyramide signal amplification (TSA) technique has been shown to detect scarce tissue antigens in light and electron microscopy. In this study we applied the TSA technique at the electron microscopic level to pre-embedding immunocytochemistry. This protocol was compared to the non-amplified protocol. With the TSA protocol, the labeling of GM130, a cis-Golgi matrix protein, was tested in a cell line and found to be highly sensitive and more enhanced than that with the simple protocol. Moreover, the gold particles were well localized to the cis-side of the Golgi apparatus in both the TSA and the simple protocol. 相似文献
957.
Kim MN Kim N Lee SH Park YS Hwang JH Kim JW Jeong SH Lee DH Kim JS Jung HC Song IS 《Helicobacter》2008,13(4):261-268
Background: This study was performed to evaluate whether the addition of probiotics to proton pump inhibitor (PPI)‐based triple therapy increases the likelihood of successful Helicobacter pylori eradication. Materials and Methods: Three hundred and forty‐seven H. pylori‐infected patients were randomized into a triple‐plus‐yogurt group (yogurt group, n = 168) or a triple‐only group (control group, n = 179). Triple therapy consisted of PPI b.i.d., clarithromycin 500 mg b.i.d., and amoxicillin 1 g b.i.d. for 7 days. Yogurt group received triple therapy for 1 week and one bottle of Will yogurt per day for at 3 weeks, starting on the first day of triple therapy. Will yogurt (a Korean brand) contains Lactobacillus acidophilus HY2177, Lactobacillus casei HY2743, Bifidobacterium longum HY8001, and Streptococcus thermophilus B‐1. 13C‐urea breath test was performed at least 4 weeks after completion of triple therapy. Eradication rates, compliances, and adverse events were compared. Results: By intention‐to treat analysis the H. pylori eradication rates in the yogurt group 79.2% (133 of 168) was similar to that in the control group 72.1% (129 of 179) (p = .124). However, by per‐protocol (PP) analysis, the eradication rate in the yogurt group, 87.5% (133 of 152) was higher than that in the control group, 78.7% (129 of 164) (p = .037). Common adverse events were metallic taste (11.8%) and diarrhea (8.6%). The frequency of adverse effects in the yogurt group 41.1% (69/168) were higher than in the control group, 26.3% (47 of 179) (p = .003). However, most adverse events were mild to moderate in intensity, and the severities of adverse effects were similar in both groups (p = .401). Conclusions: The addition of Will yogurt to triple therapy did not reduce the side‐effects of triple therapy. But it increased the H. pylori eradication rate by PP analysis, encouraging more research in this field. 相似文献
958.
Zhang J Shi X Li Y Kim BJ Jia J Huang Z Yang T Fu X Jung SY Wang Y Zhang P Kim ST Pan X Qin J 《Molecular cell》2008,31(1):143-151
Sister chromatid cohesion is normally established in S phase in a process that depends on the cohesion establishment factor Eco1, a conserved acetyltransferase. However, due to the lack of known in vivo substrates, how Eco1 regulates cohesion is not understood. Here we report that yeast Eco1 and its human ortholog, ESCO1, both acetylate Smc3, a component of the cohesin complex that physically holds the sister chromatid together, at two conserved lysine residues. Mutating these lysine residues to a nonacetylatable form leads to increased loss of sister chromatid cohesion and genome instability in both yeast and human. In addition, we clarified that the acetyltransferase activity of Eco1 is essential for its function. Our study thus identified a molecular target for the acetyltransferase Eco1 and revealed that Smc3 acetylation is a conserved mechanism in regulating sister chromatid cohesion. 相似文献
959.
960.
Hepatitis C virus (HCV) genotyping by annealing reverse transcription-PCR products with genotype-specific capture probes 总被引:1,自引:0,他引:1
Rho J Ryu JS Hur W Kim CW Jang JW Bae SH Choi JY Jang SK Yoon SK 《Journal of microbiology (Seoul, Korea)》2008,46(1):81-87
The genotype of the hepatitis C virus (HCV) strain infecting a given patient is an important predictive factor for the clinical outcome of chronic liver disease and its response to anti-viral therapeutic agents. We herein sought to develop a new easy, sensitive and accurate HCV genotyping method using annealing genotype-specific capture probes (AGSCP) in an automation-friendly 96-well plate format. The validation of our new AGSCP was performed using the Standard HCV Genotype Panel. We then used both our AGSCP and the commercially available INNO-LiPA assay to analyze the HCV genotypes from 111 Korean patients. Discordant results were analyzed by direct sequencing. AGSCP successfully genotyped the standard panel. The genotypes of 111 patient samples were also obtained successfully by AGSCP and INNO-LiPA. We observed a high concordance rate (93 matched samples, 83.8%) between the two assays. Sequencing analysis of the 18 discordant results revealed that the AGSCP had correctly identified 12 samples, whereas the INNO-LiPA had correctly identified only 6. These results collectively indicate that AGSCP assay is a convenient and sensitive method for large-scale genotyping, and it may be a promising tool for the determination of HCV and other genotypes in clinical settings. 相似文献