全文获取类型
收费全文 | 2742篇 |
免费 | 275篇 |
国内免费 | 6篇 |
专业分类
3023篇 |
出版年
2023年 | 21篇 |
2022年 | 39篇 |
2021年 | 63篇 |
2020年 | 23篇 |
2019年 | 36篇 |
2018年 | 54篇 |
2017年 | 40篇 |
2016年 | 57篇 |
2015年 | 122篇 |
2014年 | 125篇 |
2013年 | 173篇 |
2012年 | 229篇 |
2011年 | 215篇 |
2010年 | 114篇 |
2009年 | 99篇 |
2008年 | 161篇 |
2007年 | 145篇 |
2006年 | 154篇 |
2005年 | 106篇 |
2004年 | 102篇 |
2003年 | 87篇 |
2002年 | 89篇 |
2001年 | 87篇 |
2000年 | 74篇 |
1999年 | 57篇 |
1998年 | 19篇 |
1997年 | 22篇 |
1996年 | 26篇 |
1995年 | 29篇 |
1994年 | 22篇 |
1993年 | 11篇 |
1992年 | 35篇 |
1991年 | 18篇 |
1990年 | 33篇 |
1989年 | 35篇 |
1988年 | 28篇 |
1987年 | 19篇 |
1986年 | 22篇 |
1985年 | 29篇 |
1984年 | 14篇 |
1983年 | 17篇 |
1982年 | 12篇 |
1981年 | 10篇 |
1980年 | 17篇 |
1979年 | 24篇 |
1977年 | 10篇 |
1975年 | 14篇 |
1973年 | 10篇 |
1970年 | 10篇 |
1969年 | 12篇 |
排序方式: 共有3023条查询结果,搜索用时 0 毫秒
221.
Phung Khanh Lam Dong Thi Hoai Tam Nguyen Minh Dung Nguyen Thi Hanh Tien Nguyen Tan Thanh Kieu Cameron Simmons Jeremy Farrar Bridget Wills Marcel Wolbers 《PloS one》2015,10(5)
PurposeTo identify risk factors and develop a prediction model for the development of profound and recurrent shock amongst children presenting with dengue shock syndrome (DSS)MethodsWe analyzed data from a prospective cohort of children with DSS recruited at the Paediatric Intensive Care Unit of the Hospital for Tropical Disease in Ho Chi Minh City, Vietnam. The primary endpoint was “profound DSS”, defined as ≥2 recurrent shock episodes (for subjects presenting in compensated shock), or ≥1 recurrent shock episodes (for subjects presenting initially with decompensated/hypotensive shock), and/or requirement for inotropic support. Recurrent shock was evaluated as a secondary endpoint. Risk factors were pre-defined clinical and laboratory variables collected at the time of presentation with shock. Prognostic model development was based on logistic regression and compared to several alternative approaches.ResultsThe analysis population included 1207 children of whom 222 (18%) progressed to “profound DSS” and 433 (36%) had recurrent shock. Independent risk factors for both endpoints included younger age, earlier presentation, higher pulse rate, higher temperature, higher haematocrit and, for females, worse hemodynamic status at presentation. The final prognostic model for “profound DSS” showed acceptable discrimination (AUC=0.69 for internal validation) and calibration and is presented as a simple score-chart.ConclusionsSeveral risk factors for development of profound or recurrent shock among children presenting with DSS were identified. The score-chart derived from the prognostic models should improve triage and management of children presenting with DSS in dengue-endemic areas. 相似文献
222.
Lui Ng Timothy Ming-Hun Wan Colin Siu-Chi Lam Ariel Ka-Man Chow Sunny Kit-Man Wong Johnny Hon-Wai Man Hung-Sing Li Nathan Shiu-Man Cheng Ryan Chung-Hei Pak Alvin Ho-Kwan Cheung Thomas Chung-Cheung Yau Oswens Siu-Hung Lo Dominic Chi-Chung Foo Jensen Tung-Chung Poon Ronnie Tung-Ping Poon Roberta Wen-Chi Pang Wai-Lun Law 《PloS one》2015,10(5)
BackgroundThe overall prognosis of colorectal cancer (CRC) patients is unsatisfactory due to cancer metastasis after operation. This study aims to investigate the clinical significance of plasma osteopontin (OPN) levels as minimally invasive, predictive, and surrogate biomarkers for prognosis of CRC patients.MethodsThis randomized study design consists of pre-operative and post-operative plasma samples from a total of 79 patients. We determined plasma levels of OPN by ELISA and examined their correlation with the clinicopathological parameters of CRC patients. The effects of endogenous and exogenous OPN on CRC metastasis were investigated by examination of the effect on regulators of epithelial to messenchymal transition and migration assay.ResultsOur findings demonstrated for the first time the clinical correlation of plasma OPN with metastasis of CRC patients. High post-operative plasma OPN level (>153.02 ng/ml) associated with development of metastasis after curative resection (p<0.001). Moreover, post-operative plasma OPN level correlated with disease-free survival of CRC patients (p=0.009) and was an independent factor for predicting development of metastasis in CRC patients after curative resection (p=0.036). Our in vitro model showed that OPN ectopic expression induced DLD1 cell migration through Snail and Twist1 overexpression and E-cadherin repression, and secretory OPN level enhanced cell migration.ConclusionsThe results of the current study suggest that post-operative plasma OPN correlated with post-operative metastasis, suggesting that it is a potential non-invasive biomarker for the development of future metastasis in CRC patients. In addition, OPN was shown to be involved in the metastatic process and thus inhibition of OPN is a potential therapeutic approach to treat CRC patients. 相似文献
223.
Jun Ding Carlo Sidore Thomas J. Butler Mary Kate Wing Yong Qian Osorio Meirelles Fabio Busonero Lam C. Tsoi Andrea Maschio Andrea Angius Hyun Min Kang Ramaiah Nagaraja Francesco Cucca Gon?alo R. Abecasis David Schlessinger 《PLoS genetics》2015,11(7)
DNA sequencing identifies common and rare genetic variants for association studies, but studies typically focus on variants in nuclear DNA and ignore the mitochondrial genome. In fact, analyzing variants in mitochondrial DNA (mtDNA) sequences presents special problems, which we resolve here with a general solution for the analysis of mtDNA in next-generation sequencing studies. The new program package comprises 1) an algorithm designed to identify mtDNA variants (i.e., homoplasmies and heteroplasmies), incorporating sequencing error rates at each base in a likelihood calculation and allowing allele fractions at a variant site to differ across individuals; and 2) an estimation of mtDNA copy number in a cell directly from whole-genome sequencing data. We also apply the methods to DNA sequence from lymphocytes of ~2,000 SardiNIA Project participants. As expected, mothers and offspring share all homoplasmies but a lesser proportion of heteroplasmies. Both homoplasmies and heteroplasmies show 5-fold higher transition/transversion ratios than variants in nuclear DNA. Also, heteroplasmy increases with age, though on average only ~1 heteroplasmy reaches the 4% level between ages 20 and 90. In addition, we find that mtDNA copy number averages ~110 copies/lymphocyte and is ~54% heritable, implying substantial genetic regulation of the level of mtDNA. Copy numbers also decrease modestly but significantly with age, and females on average have significantly more copies than males. The mtDNA copy numbers are significantly associated with waist circumference (p-value = 0.0031) and waist-hip ratio (p-value = 2.4×10-5), but not with body mass index, indicating an association with central fat distribution. To our knowledge, this is the largest population analysis to date of mtDNA dynamics, revealing the age-imposed increase in heteroplasmy, the relatively high heritability of copy number, and the association of copy number with metabolic traits. 相似文献
224.
Partially Redundant Enhancers Cooperatively Maintain Mammalian Pomc Expression Above a Critical Functional Threshold 总被引:1,自引:0,他引:1
225.
In recent decades, several Western countries have reported an increase in oropharyngeal and anal cancers caused by human papillomavirus (HPV). Trends in HPV-associated cancers in Asia have not been as well described. We describe the epidemiology of potentially HPV-related cancers reported to the Singapore Cancer Registry from 1968–2012. Analysis included 998 oropharyngeal squamous cell carcinoma (OPSCC), 183 anal squamous cell carcinoma (ASCC) and 8,019 invasive cervical cancer (ICC) cases. Additionally, 368 anal non-squamous cell carcinoma (ANSCC) and 2,018 non-oropharyngeal head and neck carcinoma (non-OP HNC) cases were included as comparators. Age-standardized incidence rates (ASR) were determined by gender and ethnicity (Chinese, Malay and Indian). Joinpoint regression was used to evaluate annual percentage change (APC) in incidence. OPSCC incidence increased in both genders (men 1993–2012, APC = 1.9%, p<0.001; women 1968–2012, APC = 2.0%, p = 0.01) and was 5 times higher in men than women. In contrast, non-OP HNC incidence declined between 1968–2012 among men (APC = -1.6%, p<0.001) and women (APC = -0.4%, p = 0.06). ASCC and ANSCC were rare (ASR = 0.2 and 0.7 per 100,000 person-years, respectively) and did not change significantly over time except for increasing ANSCCs in men (APC = 2.8%, p<0.001). ICC was the most common HPV-associated cancer (ASR = 19.9 per 100,000 person-years) but declined significantly between 1968–2012 (APC = -2.4%). Incidence of each cancer varied across ethnicities. Similar to trends in Western countries, OPSCC incidence increased in recent years, while non-OP HNC decreased. ICC remains the most common HPV-related cancer in Singapore, but Pap screening programs have led to consistently decreasing incidence. 相似文献
226.
Development and manufacturability assessment of chemically‐defined medium for the production of protein therapeutics in CHO cells 下载免费PDF全文
Wai Lam W. Ling Yunling Bai Cheng Cheng Ishai Padawer Changjian Wu 《Biotechnology progress》2015,31(5):1163-1171
Advantages of using internally developed chemically‐defined (CD) media for cell culture‐based therapeutic protein production over commercial media include better raw material control and medium vendor options, and most importantly, flexibility for process development and subsequent optimization needed for therapeutic protein production. Through several rounds of design of experiment (DOE) screening, and medium component supplementation and optimization studies, we successfully developed a CD basal medium (CDM) for CHO cell culture. The internally prepared liquid CDM demonstrated comparable cell culture performance to that from a commercially available control medium. However, when the same CDM formulation was transferred to two major commercial medium suppliers for manufacturing, cell culture performance utilizing these newly prepared media was significantly reduced compared with the in‐house prepared counterpart. An investigation was launched to assess whether key medium components were sensitive to large‐scale preparation of the final bulk media by the vendors. Further work necessitated the reformulation of the original CDM formulation into a core medium that was suitable for large‐scale media manufacturing. The modified preparation of the core medium with two separate supplements to generate the final CDM was able to recover the expected cell culture performance and monoclonal antibody (mAb) productivity. Confirmation of cell culture robustness in cell growth and production was corroborated in two additional mAb‐expressing cell lines. This work demonstrates that a robust CD medium is not only one that performs during the development stage, but also one that must be reproducible by commercial media vendors. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1163–1171, 2015 相似文献
227.
Christopher T. Lam Marlee S. Krieger Jennifer E. Gallagher Betsy Asma Lisa C. Muasher John W. Schmitt Nimmi Ramanujam 《PloS one》2015,10(9)
Introduction
Current guidelines by WHO for cervical cancer screening in low- and middle-income countries involves visual inspection with acetic acid (VIA) of the cervix, followed by treatment during the same visit or a subsequent visit with cryotherapy if a suspicious lesion is found. Implementation of these guidelines is hampered by a lack of: trained health workers, reliable technology, and access to screening facilities. A low cost ultra-portable Point of Care Tampon based digital colposcope (POCkeT Colposcope) for use at the community level setting, which has the unique form factor of a tampon, can be inserted into the vagina to capture images of the cervix, which are on par with that of a state of the art colposcope, at a fraction of the cost. A repository of images to be compiled that can be used to empower front line workers to become more effective through virtual dynamic training. By task shifting to the community setting, this technology could potentially provide significantly greater cervical screening access to where the most vulnerable women live. The POCkeT Colposcope’s concentric LED ring provides comparable white and green field illumination at a fraction of the electrical power required in commercial colposcopes. Evaluation with standard optical imaging targets to assess the POCkeT Colposcope against the state of the art digital colposcope and other VIAM technologies.Results
Our POCkeT Colposcope has comparable resolving power, color reproduction accuracy, minimal lens distortion, and illumination when compared to commercially available colposcopes. In vitro and pilot in vivo imaging results are promising with our POCkeT Colposcope capturing comparable quality images to commercial systems.Conclusion
The POCkeT Colposcope is capable of capturing images suitable for cervical lesion analysis. Our portable low cost system could potentially increase access to cervical cancer screening in limited resource settings through task shifting to community health workers. 相似文献228.
Jane Topolovec-Vranic Stanley Zhang Hatty Wong Emily Lam Rowan Jing Kelly Russell Michael D. Cusimano Canadian Brain Injury Violence Research Team 《PloS one》2015,10(11)
Objective
To evaluate the awareness of concussion-related symptoms amongst members of the sports community in Canada.Methods
A cross-sectional national electronic survey was conducted. Youth athletes, parents, coaches and medical professionals across Canada were recruited through mailing lists from sports-related opt-in marketing databases. Participants were asked to identify, from a list of options, the symptoms of a concussion. The proportion of identified symptoms (categorized as physical, cognitive, mental health-related and overall) as well as participant factors associated with symptom recognition were analyzed.Results
The survey elicited 6,937 responses. Most of the respondents (92.1%) completed the English language survey, were male (57.7%), 35–54 years of age (61.7%), with post-secondary education (58.2%), or high reported yearly household income (>$80,000; 53.0%). There were respondents from all provinces and territories with the majority of respondents from Ontario (35.2%) or British Columbia (19.1%). While participants identified most of the physical (mean = 84.2% of symptoms) and cognitive (mean = 91.2% of symptoms), they on average only identified 53.5% of the mental health-related symptoms of concussions. Respondents who were older, with higher education and household income, or resided in the Northwest Territories or Alberta identified significantly more of the mental health-related symptoms listed.Interpretation
While Canadian youth athletes, parents, coaches and medical professionals are able to identify most of the physical and cognitive symptoms associated with concussion, identification of mental health-related symptoms of concussion is still lagging. 相似文献229.
Yangbo Sun Chao Qiang Jiang Kar Keung Cheng Wei Sen Zhang Gabriel M. Leung Tai Hing Lam C. Mary Schooling 《PloS one》2015,10(8)
Objective
To examine the adjusted associations of fruit consumption and vegetable consumption with the Framingham score and its components in the non-Western setting of Southern China, considering health status.Method
Linear regression was used to assess the cross-sectional associations of fruit and vegetable consumption with the Framingham score and its components, among 19,518 older Chinese (≥50 years) from the Guangzhou Biobank Cohort Study in Southern China (2003–2006), and whether these differed by health status.Results
The association of fruit consumption with the Framingham score varied by health status (P-value<0.001), but not vegetable consumption (P-value 0.51). Fruit consumption was associated with a lower Framingham score (-0.04 per portions/day, 95% confidence interval (CI) -0.08 to -0.004) among participants in poor health, adjusted for age, sex, recruitment phase, socio-economic position and lifestyle. However, similarly adjusted, fruit consumption was associated with a higher Framingham score (0.05, 95% CI 0.02 to 0.09) among participants in good health, perhaps due to a positive association of fruit consumption with fasting glucose. Similarly adjusted, vegetable consumption was associated with a higher Framingham score (0.03, 95% CI 0.01 to 0.05) among all participants, with no difference by health status.Conclusion
This large study from a non-western setting found that fruit and vegetable consumption was barely associated with the Framingham score, or major CVD risk factors. 相似文献230.
Alan C. H. Lee Joanne K. Y. Lam Sammy W. M. Shiu Ying Wong D. John Betteridge Kathryn C. B. Tan 《PloS one》2015,10(9)