全文获取类型
收费全文 | 12160篇 |
免费 | 780篇 |
国内免费 | 7篇 |
出版年
2024年 | 15篇 |
2023年 | 39篇 |
2022年 | 138篇 |
2021年 | 233篇 |
2020年 | 131篇 |
2019年 | 205篇 |
2018年 | 295篇 |
2017年 | 244篇 |
2016年 | 427篇 |
2015年 | 618篇 |
2014年 | 754篇 |
2013年 | 801篇 |
2012年 | 1077篇 |
2011年 | 1047篇 |
2010年 | 652篇 |
2009年 | 501篇 |
2008年 | 791篇 |
2007年 | 677篇 |
2006年 | 615篇 |
2005年 | 563篇 |
2004年 | 574篇 |
2003年 | 460篇 |
2002年 | 364篇 |
2001年 | 355篇 |
2000年 | 327篇 |
1999年 | 227篇 |
1998年 | 90篇 |
1997年 | 77篇 |
1996年 | 50篇 |
1995年 | 48篇 |
1994年 | 38篇 |
1993年 | 30篇 |
1992年 | 83篇 |
1991年 | 54篇 |
1990年 | 44篇 |
1989年 | 48篇 |
1988年 | 27篇 |
1987年 | 28篇 |
1986年 | 21篇 |
1985年 | 23篇 |
1984年 | 13篇 |
1983年 | 15篇 |
1982年 | 12篇 |
1981年 | 12篇 |
1980年 | 11篇 |
1979年 | 9篇 |
1978年 | 15篇 |
1975年 | 13篇 |
1974年 | 11篇 |
1970年 | 6篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
181.
Jae-Yoo Choi Yong-Dae Gwon Jeong-Ki Kim Yeon-Dong Cho Yoon-Ki Heo Han-Sam Cho Tae-Jin Choi Ha-Ryoung Poo Yu-Kyoung Oh Young Bong Kim 《PloS one》2013,8(11)
Despite the advantages of DNA vaccines, overcoming their lower efficacy relative to that of conventional vaccines remains a challenge. Here, we constructed a human endogenous retrovirus (HERV) envelope-coated, nonreplicable, baculovirus-based HA vaccine against swine influenza A/California/04/2009(H1N1) hemagglutin (HA) (AcHERV-sH1N1-HA) as an alternative to conventional vaccines and evaluated its efficacy in two strains of mice, BALB/c and C57BL/6. A commercially available, killed virus vaccine was used as a positive control. Mice were intramuscularly administered AcHERV-sH1N1-HA or the commercial vaccine and subsequently given two booster injections. Compared with the commercial vaccine, AcHERV-sH1N1-HA induced significantly higher levels of cellular immune responses in both BALB/c and C57BL/6 mice. Unlike cellular immune responses, humoral immune responses depended on the strain of mice. Following immunization with AcHERV-sH1N1-HA, C57BL/6 mice showed HA-specific IgG titers 10- to 100-fold lower than those of BALB/c mice. In line with the different levels of humoral immune responses, the survival of immunized mice after intranasal challenge with sH1N1 virus (A/California/04/2009) depended on the strain. After challenge with 10-times the median lethal dose (MLD50) of sH1N1 virus, 100% of BALB/c mice immunized with the commercial vaccine or AcHERV-sH1N1-HA survived. In contrast, C57BL/6 mice immunized with AcHERV-sH1N1-HA or the commercial vaccine showed 60% and 70% survival respectively, after challenge with sH1N1 virus. In all mice, virus titers and results of histological analyses of lung tissues were consistent with the survival data. Our results indicate the importance of humoral immune response as a major defense system against influenza viral infection. Moreover, the complete survival of BALB/c mice immunized with AcHERV-sH1N1-HA after challenge with sH1N1 virus suggests the potential of baculoviral vector-based vaccines to achieve an efficacy comparable to that of killed virus vaccines. 相似文献
182.
Seung-Hwan Jeong Dong-Hun Lee Byoung-Yoon Kim Soo-Won Choi Joong-Bok Lee Seung-Yong Park In-Soo Choi Chang-Seon Song 《PloS one》2013,8(12)
Newcastle disease (ND) is one of the most devastating poultry infections because of its worldwide distribution and accompanying economical threat. In the present study, we characterized the ND virus (NDV) K148/08 strain from wild mallard duck, with regard to safety, thermostability, immunogenicity, and protective efficacy against velogenic ND viral infection. The NDV K148/08 strain offered enhanced immunogenicity and safety relative to commercially available vaccine strains. The NDV K148/08 strain was safe in 1-day-old SPF chicks after vaccination using a coarse or cabinet-type fine sprayer. We demonstrated that the NDV K148/08 strain elicited high levels of antibody responses and provided protective efficacy against lethal NDV challenge. In addition, the thermostability of the NDV K148/08 strain was as high as that of the thermostable V4 strain. Therefore, the NDV K148/08 strain may be useful to ensure NDV vaccine performance and effectiveness in developing countries, especially in remote areas without cold chains. 相似文献
183.
Abdul Roouf Bhat Mohammad Arshad Eun Ju Lee Smritee Pokharel Inho Choi Fareeda Athar 《化学与生物多样性》2013,10(12):2267-2277
A new series of N‐(pyrimidin‐2‐yl)benzenesulfonamide derivatives, 3a – 3i and 4a – 4i , was synthesized from pyrimidin‐2‐amines, 2a – 2i , with the aim to explore their effects on in vitro growth of Entamoeba histolytica. The chemical structures of the compounds were elucidated by elemental analysis, FT‐IR, 1H‐ and 13C‐NMR, and ESI mass‐spectral data. In vitro anti‐amoebic activity was evaluated against HM1 : IMSS strain of Entamoeba histolytica. The IC50 values were calculated by using the double dilution method. The results were compared with the IC50 value of the standard drug ‘metronidazole’. The selected compounds were tested for their cytotoxic activities by cell‐viability assay using H9C2 cardiac myoblasts cell line, and the results indicated that all the compounds displayed remarkable >80% viabilities to a concentration of 100 μg/ml. 相似文献
184.
Seok-In Yun Seong-Joo Gang Hee-Myong Ro Min-Jin Lee Woo-Jung Choi Seong-Gu Hong Kwon-Kyoo Kang 《Bioprocess and biosystems engineering》2013,36(5):591-595
Conversion of synthesis gas (CO and H2) to ethanol can be an alternative, promising technology to produce biofuels from renewable biomass. To distinguish microbial utilization of carbon source between fructose and synthesis gas CO and to evaluate biological production of ethanol from CO, we adopted the 13C-enrichment of the CO substrate and hypothesized that the residual increase in δ13C of the cell biomass would reflect the increased contribution of 13C-enriched CO. Addition of synthesis gas to live culture medium for ethanol fermentation by Clostridum ljungdahlii increased the microbial growth and ethanol production. Despite the high 13C-enrichment in CO (99 atom % 13C), however, microbial δ13C increased relatively small compared to the microbial growth. The uptake efficiency of CO estimated using the isotope mass balance equation was also very low: 0.0014 % for the low CO and 0.0016 % for the high CO treatment. Furthermore, the fast production of ethanol in the early stage indicated that the presence of sugar in fermentation medium would limit the utilization of CO as a carbon source by C. ljungdahlii. 相似文献
185.
Jung Ok Park Do‐Young Choi Dong‐Sic Choi Hee Joung Kim Jeong Won Kang Jae Hun Jung Jeong Hwa Lee Jayoung Kim Michael R. Freeman Kye Young Lee Yong Song Gho Kwang Pyo Kim 《Proteomics》2013,13(14):2125-2134
Microvesicles (MVs, also known as exosomes, ectosomes, microparticles) are released by various cancer cells, including lung, colorectal, and prostate carcinoma cells. MVs released from tumor cells and other sources accumulate in the circulation and in pleural effusion. Although recent studies have shown that MVs play multiple roles in tumor progression, the potential pathological roles of MV in pleural effusion, and their protein composition, are still unknown. In this study, we report the first global proteomic analysis of highly purified MVs derived from human nonsmall cell lung cancer (NSCLC) pleural effusion. Using nano‐LC–MS/MS following 1D SDS‐PAGE separation, we identified a total of 912 MV proteins with high confidence. Three independent experiments on three patients showed that MV proteins from PE were distinct from MV obtained from other malignancies. Bioinformatics analyses of the MS data identified pathologically relevant proteins and potential diagnostic makers for NSCLC, including lung‐enriched surface antigens and proteins related to epidermal growth factor receptor signaling. These findings provide new insight into the diverse functions of MVs in cancer progression and will aid in the development of novel diagnostic tools for NSCLC. 相似文献
186.
Woo Young Jeon Woo Yong Shim Sung Hyeon Lee Joon Ho Choi Jung Hoe Kim 《Bioprocess and biosystems engineering》2013,36(6):809-817
Xylose utilization is inhibited by glucose uptake in xylose-assimilating yeasts, including Candida tropicalis, resulting in limitation of xylose uptake during the fermentation of glucose/xylose mixtures. In this study, a heterologous xylose transporter gene (At5g17010) from Arabidopsis thaliana was selected because of its high affinity for xylose and was codon-optimized for functional expression in C. tropicalis. The codon-optimized gene was placed under the control of the GAPDH promoter and was integrated into the genome of C. tropicalis strain LXU1 which is xyl2-disrupted and NXRG (codon-optimized Neurospora crassa xylose reductase) introduced. The xylose uptake rate was increased by 37–73 % in the transporter expression-enhanced strains depending on the glucose/xylose mixture ratio. The recombinant strain LXT2 in 500-mL flask culture using glucose/xylose mixtures showed a xylose uptake rate that was 29 % higher and a xylitol volumetric productivity (1.14 g/L/h) that was 25 % higher than the corresponding rates for control strain LXU1. Membrane protein extraction and Western blot analysis confirmed the successful heterologous expression and membrane localization of the xylose transporter in C. tropicalis. 相似文献
187.
188.
Mark Lucock Zo? Yates Charlotte Martin Jeong-Hwa Choi Lyndell Boyd Sa Tang Nenad Naumovski Paul Roach Martin Veysey 《Genes & nutrition》2013,8(2):221-229
Hydrogen sulphide (H2S) is a gaseous signalling molecule that regulates blood flow and pressure. It is synthesised from cysteine via cystathionine β-synthase and cystathionine γ-lyase. We examined whether thiol precursors of H2S, transsulphuration pathway gene variants (CBS-844ins68 and CTH-G1364T) and key B-vitamin cofactors might be critical determinants of hypertension in an elderly Australian population. An elderly Australian retirement village population (n = 228; age 65–96 years, 91 males and 137 females) was assessed for the prevalence of two transsulphuration pathway–related variant genes associated with cysteine synthesis and hence H2S production. Thiols were determined by HPLC, genotypes by PCR and dietary intake by food frequency questionnaire. Homocysteine levels were statistically higher in the hypertensive phenotype (p = 0.0399), but there was no difference for cysteine or glutathione. Using nominal logistic regression, cysteine, CTH-G1364T genotype, dietary synthetic folate and vitamin B6 predicted clinical phenotype (determined as above/below 140/90 mm Hg) and then only in female subjects (p = 0.0239, 0.0178, 0.0249 and 0.0371, respectively). Least-squares regression supports cysteine being highly inversely predictive of diastolic blood pressure: p and r 2 values <0.0001 and 0.082; 0.0409 and 0.046; and <0.0001 and 0.113 for all subjects, males and females, respectively. Additionally, CTH-G1364T genotype predicts diastolic blood pressure in males (p = 0.0217; r 2 = 0.083), but contrasts with observations for females. Overall, analyses, including stepwise regression, suggest cysteine, dietary natural and synthetic folate, vitamins B6 and B12, and both genetic variants (CTH-C1364T and CBS-844ins68) are all aetiologically relevant in the regulation of blood pressure. Hydrogen sulphide is a vasorelaxant gasotransmitter with characteristics similar to nitric oxide. Cysteine and the G1364T and 844ins68 variants of the cystathionine γ-lyase and cystathionine β-synthase genes, respectively, are the biological determinants of H2S synthesis, and all three are shown here to influence the hypertensive phenotype. Additionally, B-vitamin cofactors for these three enzymes may also be important determinants of blood pressure. 相似文献
189.
Hyunsoo Kim Taesoo Kim Byung-Chul Jeong Il-Taeg Cho Daehee Han Noriko Takegahara Takako Negishi-Koga Hiroshi Takayanagi Jae Hee Lee Jai-Yoon Sul Vikram Prasad Seoung Hoon Lee Yongwon Choi 《Cell metabolism》2013,17(2):249-260
Highlights? Tmem64-deficient mice show increased bone volume ? Tmem64 deficiency reduces [Ca2+]i oscillation in response to RANKL stimulation ? Tmem64 interacts with SERCA2 ? Tmem64 positively regulates osteoclast formation via SERCA2/Ca2+ signaling 相似文献
190.
Hoon-Ki Sung Kyung-Oh Doh Joe Eun Son Jin Gyoon Park Yunui Bae Soojeong Choi Seana Mary Lunney Nelson Rebecca Cowling Kristina Nagy Iacovos P. Michael Gou Young Koh S. Lee Adamson Tony Pawson Andras Nagy 《Cell metabolism》2013,17(1):61-72
Highlights? Two-way modulations of adipose VEGF were generated with aP2-Cre transgene ? Adipose VEGF KO reduces vasculature, increases hypoxia and inflammation in fat ? Adipose VEGF KO accelerates the development of metabolic disease in high-fat diet ? Induced adipose VEGF has opposite effect on fat and restores metabolic homeostasis 相似文献