全文获取类型
收费全文 | 18762篇 |
免费 | 1720篇 |
国内免费 | 600篇 |
出版年
2023年 | 203篇 |
2022年 | 250篇 |
2021年 | 666篇 |
2020年 | 601篇 |
2019年 | 702篇 |
2018年 | 796篇 |
2017年 | 544篇 |
2016年 | 818篇 |
2015年 | 1140篇 |
2014年 | 1294篇 |
2013年 | 1458篇 |
2012年 | 1756篇 |
2011年 | 1548篇 |
2010年 | 957篇 |
2009年 | 847篇 |
2008年 | 1068篇 |
2007年 | 933篇 |
2006年 | 822篇 |
2005年 | 731篇 |
2004年 | 583篇 |
2003年 | 542篇 |
2002年 | 471篇 |
2001年 | 357篇 |
2000年 | 294篇 |
1999年 | 284篇 |
1998年 | 170篇 |
1997年 | 132篇 |
1996年 | 95篇 |
1995年 | 106篇 |
1994年 | 75篇 |
1993年 | 66篇 |
1992年 | 94篇 |
1991年 | 94篇 |
1990年 | 85篇 |
1989年 | 66篇 |
1988年 | 53篇 |
1987年 | 51篇 |
1986年 | 38篇 |
1985年 | 43篇 |
1984年 | 21篇 |
1983年 | 23篇 |
1982年 | 19篇 |
1981年 | 11篇 |
1979年 | 18篇 |
1978年 | 16篇 |
1977年 | 19篇 |
1976年 | 15篇 |
1975年 | 14篇 |
1972年 | 15篇 |
1969年 | 10篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
P. Bourke D. Ziuzina L. Han P.J. Cullen B.F. Gilmore 《Journal of applied microbiology》2017,123(2):308-324
There is a diverse range of microbiological challenges facing the food, healthcare and clinical sectors. The increasing and pervasive resistance to broad‐spectrum antibiotics and health‐related concerns with many biocidal agents drives research for novel and complementary antimicrobial approaches. Biofilms display increased mechanical and antimicrobial stability and are the subject of extensive research. Cold plasmas (CP) have rapidly evolved as a technology for microbial decontamination, wound healing and cancer treatment, owing to the chemical and bio‐active radicals generated known collectively as reactive oxygen and nitrogen species. This review outlines the basics of CP technology and discusses the interactions with a range of microbiological targets. Advances in mechanistic insights are presented and applications to food and clinical issues are discussed. The possibility of tailoring CP to control specific microbiological challenges is apparent. This review focuses on microbiological issues in relation to food‐ and healthcare‐associated human infections, the role of CP in their elimination and the current status of plasma mechanisms of action. 相似文献
2.
Soo Min Han Byungjin Hwang Tae-gun Park Do-Il Kim Moo-Yong Rhee Byoung-Kwon Lee Young Keun Ahn Byung Ryul Cho Jeongtaek Woo Seung-Ho Hur Jin-Ok Jeong Sungha Park Yangsoo Jang Min Goo Lee Duhee Bang Ji Hyun Lee Sang-Hak Lee 《PloS one》2015,10(5)
Familial hypercholesterolemia (FH) is a genetic disorder with an increased risk of early-onset coronary artery disease. Although some clinically diagnosed FH cases are caused by mutations in LDLR, APOB, or PCSK9, mutation detection rates and profiles can vary across ethnic groups. In this study, we aimed to provide insight into the spectrum of FH-causing mutations in Koreans. Among 136 patients referred for FH, 69 who met Simon Broome criteria with definite family history were enrolled. By whole-exome sequencing (WES) analysis, we confirmed that the 3 known FH-related genes accounted for genetic causes in 23 patients (33.3%). A substantial portion of the mutations (19 of 23 patients, 82.6%) resulted from 17 mutations and 2 copy number deletions in LDLR gene. Two mutations each in the APOB and PCSK9 genes were verified. Of these anomalies, two frameshift deletions in LDLR and one mutation in PCSK9 were identified as novel causative mutations. In particular, one novel mutation and copy number deletion were validated by co-segregation in their relatives. This study confirmed the utility of genetic diagnosis of FH through WES. 相似文献
3.
Yao Zhu Xiao-Qun Yang Cheng-Tao Han Bo Dai Hai-Liang Zhang Guo-Hai Shi Chao-Fu Wang Ding-Wei Ye 《PloS one》2015,10(3)
There has been a rapid increase in the incidence of prostate cancer in China, especially in areas with boosted economic development. In this study, we analyzed the pathological features of a contemporary series of radical prostatectomy cases. A total of 230 consecutive, whole-mounted radical prostatectomy specimens collected from 2012 to 2014 were reviewed. The median age of the patients was 68 years, and 64.3% of patients presented with prostate specific antigen alone. Pathological examination indicated that a high proportion (77.4%) of patients had intermediate- or high-risk disease according to the Cancer of the Prostate Risk Assessment Post-Surgical score. After surgery, only 28 patients met the criteria for active surveillance (organ-confined Gleason ≥6 disease). The Prostate Cancer Research International Active Surveillance criteria achieved a sensitivity of 57.1% and a specificity of 98.0% for identifying candidates. The probability of Gleason score upgrading was 24.8% in the entire group and 59.0% in biopsy-confirmed Gleason ≥6 disease. The predominant tumor was located in the transition zone in 14.8% of cases, while only three patients (1.3%) had a predominant tumor located in the anterior region. Patients with transition zone-predominant tumor were likely to have been referred with urinary symptoms and high prostate specific antigen levels. The results of this study highlight the contemporary pathological features of localized prostate cancer in urban China. There was an increased trend towards asymptomatic cases, though most patients had intermediate- or high-risk disease and were suitable for definitive treatment. The low prevalence of dominant cancer in the anterior region may reflect race-based pathological differences. 相似文献
4.
Shiping Yang Shaomin Lin Qiang Fu Baizhen Cai Fei Kong Guang Huang Fafen Li Han Wang 《PloS one》2015,10(3)
Background
Guidelines from the U.S. National Comprehensive Cancer Network have recommended use of concurrent chemoradiotherapy (CCRT), followed by a 3-cycles combination of platinum and 5-fluorouracil chemotherapy as standard treatment for nasopharyngeal carcinoma (NPC). The benefits of CCRT for treatment of locally advanced NPC have been established. Whether platinum and 5-fluorouracil chemotherapy should be routinely added to locally advanced NPC after CCRT is still open to debate. Whether adjuvant chemotherapy provides an additional survival benefit for the subgroup of patients with residual nasopharyngeal carcinoma who have undergone CCRT is also unclear. This retrospective study was initiated to determine the survival benefit of adjuvant chemotherapy (AC) in residual NPC patients who have undergone concurrent chemoradiotherapy.Methods
The retrospective study included 155 nasopharyngeal carcinoma patients who had local residual lesions after the platinum-based CCRT without or with AC. Kaplan-Meier analysis and the log-rank test were used to estimate overall survival (OS), failure-free survival (FFS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS).Results
Median follow-up was 47 months. Adjuvant cisplatin or nedaplatin plus 5-fluorouracil chemotherapy did not significantly improve 3-year OS, LRFS, FFS, and DMFS for patients with residual nasopharyngeal carcinoma after undergoing CCRT. The 3-year OS rates for the no-AC group and AC group were 71.6% and 73.7%, respectively (P= 0.44). The 3-year FFS rates for no-AC group and AC group were 57.5% and 66.9%, respectively ((P= 0.19). The 3-year LRFS rates for no-AC group and AC group were 84.7% and 87.9%, respectively ((P= 0.51). The 3-year DMFS rates for no-AC group and AC group were 71.4% and 77.4%, respectively ((P= 0.23).Conclusions
Since we did not find sufficient data to support significant survival in 3-year OS, LRFS, FFS, and DMFS, whether Adjuvant cisplatin or nedaplatin and 5-fluorouracil chemotherapy should be routinely added to residual nasopharyngeal carcinoma patients after undergoing CCRT remain uncertain. 相似文献5.
6.
Won Choi Jae Chan Kim Won Soo Kim Han Jin Oh Jee Myung Yang Jee Bum Lee Kyung Chul Yoon 《PloS one》2015,10(10)
Purpose
To investigate the clinical efficacy and safety of wearable antioxidant glasses containing extracts of medicinal plants in patients with mild dry eye disease (DED).Methods
Fifty patients with mild DED were randomly assigned to wear either extracts of antioxidant medicinal plants containing (N = 25) or placebo glasses (N = 25). Patients wore the glasses for 15 min three times daily. The ocular surface disease index (OSDI) score, tear film break up time (BUT), and Schirmer’s test were evaluated and compared within the group and between the groups at baseline, 4 weeks, and 8 weeks after treatment.Results
OSDI score and tear film BUT were significantly improved in the treatment group at 4 and 8 weeks after wearing glasses (all P < 0.001). Compared to the placebo group, the OSDI scores were significantly lower in the treatment group at 8 weeks (P = 0.007). The results of the Schirmer’s test showed significant improvement in the treatment group at 4 weeks (P = 0.035), however there were no significant differences between the other groups or within the groups. No adverse events were reported during the study.Conclusions
Antioxidant glasses containing extracts of medicinal plants were effective in improving in DED both subjectively and objectively. Wearing antioxidants glasses might be a safe and adjunctive therapeutic option for DED.Trial Registration
ISRCTN registry 71217488 相似文献7.
8.
Sisi Patricia Lolita Ameria Hye Sook Jung Hee Sook Kim Sang Soo Han Hak Sung Kim Jin Ho Lee 《Biotechnology letters》2015,37(8):1637-1644
Objective
To examine the role of a gene encoding flavin-containing monooxygenase (cFMO) from Corynebacterium glutamicum ATCC13032 when cloned and expressed in Escherichia coli for the production of indigo pigments.Results
The blue pigments produced by recombinant E. coli were identified as indigo and indirubin. The cFMO was purified as a fused form with maltose-binding protein (MBP). The enzyme was optimal at 25 °C and pH 8. From absorption spectrum analysis, the cFMO was classified as a flavoprotein. FMO activity was strongly inhibited by 1 mM Cu2+ and recovered by adding 1–10 mM EDTA. The enzyme catalyzed the oxidation of TMA, thiourea, and cysteamine, but not glutathione or cysteine. MBP-cFMO had an indole oxygenase activity through oxygenation of indole to indoxyl. The recombinant E. coli produced 685 mg indigo l?1 and 103 mg indirubin l?1 from 2.5 g l-tryptophan l?1.Conclusion
The results suggest the cFMO can be used for the microbial production of both indigo and indirubin.9.
α‐ l‐iduronidase gene‐based therapy using the phiC31 system to treat mucopolysaccharidose type I mice 下载免费PDF全文
Roberta Sessa Stilhano Priscila Keiko Matsumoto Martin Suely Maymone de Melo Vivian Yochiko Samoto Giovani Bravin Peres Yara Maria Correa da Silva Michelacci Flavia Helena da Silva Vanessa Gonçalves Pereira Vania D'Almeida Adriana Taveira da Cruz Miriam Galvonas Jasiulionis Sang Won Han 《The journal of gene medicine》2015,17(1-2):1-13
10.
Dae Won Kim Sung Ho Lee Min Jea Shin Kibom Kim Sae Kwang Ku Jong Kyu Youn Su Bin Cho Jung Hwan Park Chi Hern Lee Ora Son Eun Jeong Sohn Sung-Woo Cho Jong Hoon Park Hyun Ah Kim Kyu Hyung Han Jinseu Park Won Sik Eum Soo Young Choi 《BMB reports》2015,48(11):618-623
FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In the cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI. [BMB Reports 2015; 48(11): 618-623] 相似文献