全文获取类型
收费全文 | 2785篇 |
免费 | 201篇 |
国内免费 | 150篇 |
专业分类
3136篇 |
出版年
2023年 | 21篇 |
2022年 | 57篇 |
2021年 | 109篇 |
2020年 | 75篇 |
2019年 | 94篇 |
2018年 | 104篇 |
2017年 | 78篇 |
2016年 | 86篇 |
2015年 | 161篇 |
2014年 | 163篇 |
2013年 | 221篇 |
2012年 | 228篇 |
2011年 | 189篇 |
2010年 | 134篇 |
2009年 | 115篇 |
2008年 | 98篇 |
2007年 | 115篇 |
2006年 | 112篇 |
2005年 | 116篇 |
2004年 | 109篇 |
2003年 | 81篇 |
2002年 | 59篇 |
2001年 | 65篇 |
2000年 | 55篇 |
1999年 | 55篇 |
1998年 | 28篇 |
1997年 | 26篇 |
1996年 | 23篇 |
1995年 | 29篇 |
1994年 | 27篇 |
1993年 | 19篇 |
1992年 | 40篇 |
1991年 | 30篇 |
1990年 | 18篇 |
1989年 | 22篇 |
1988年 | 15篇 |
1987年 | 11篇 |
1986年 | 13篇 |
1985年 | 15篇 |
1984年 | 17篇 |
1983年 | 17篇 |
1982年 | 15篇 |
1981年 | 8篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1977年 | 6篇 |
1976年 | 8篇 |
1975年 | 8篇 |
1974年 | 7篇 |
1971年 | 8篇 |
排序方式: 共有3136条查询结果,搜索用时 9 毫秒
141.
142.
EUDOC is a docking program that has successfully predicted small-molecule-bound protein complexes and identified drug leads from chemical databases. To expand the application of the EUDOC program to supramolecular chemistry, we tested its ability to reproduce crystal structures of small-molecule complexes. Of 161 selected crystal structures of small-molecule guest-host complexes, EUDOC reproduced all these crystal structures with guest structure mass-weighted root mean square deviations (mwRMSDs) of <1.0 A relative to the corresponding crystal structures. In addition, the average interaction energy of these 161 guest-host complexes (-50.1 kcal/mol) was found to be nearly half of that of 153 previously tested small-molecule-bound protein complexes (-108.5 kcal/mol), according to the interaction energies calculated by EUDOC. 31 of the 161 complexes could not be reproduced with mwRMSDs of <1.0 A if neighboring hosts in the crystal structure of a guest-host complex were not included as part of the multimeric host system, whereas two of the 161 complexes could not be reproduced with mwRMSDs of <1.0 A if water molecules were excluded from the host system. These results demonstrate the significant influence of crystal packing on small molecule complexation and suggest that EUDOC is able to predict small-molecule complexes and that it is useful for the design of new materials, molecular sensors, and multimeric inhibitors of protein-protein interactions. 相似文献
143.
Lijuan Sun Sanjay Verma Navin Michael Siew Pang Chan Jianhua Yan Suresh Anand Sadananthan Stefan G. Camps Hui Jen Goh Priya Govindharajulu John Totman David Townsend Julian Pak‐Nam Goh Lei Sun Bernhard Otto Boehm Su Chi Lim Siew Kwan Sze Christiani Jeyakumar Henry Houchun Harry Hu S. Sendhil Velan Melvin Khee‐Shing Leow 《Obesity (Silver Spring, Md.)》2019,27(9):1434-1442
144.
Zhuoyang Fan Cheng Chen Xiaoying Pang Zhou Yu Yang Qi Xinyi Chen Huihui Liang Xiaoling Fang Xianyi Sha 《PloS one》2015,10(4)
Genexol-PM, produced by Samyang Company (Korea) is an excellent preparation of paclitaxel (PTX) for clinical cancer treatment. However, it cannot resolve the issue of multidrug resistance (MDR)—a significant problem in the administration of PTX to cancer patients. To increase the efficacy of Genexol-PM against MDR tumors, a mixed micelle capable of serving as a vehicle for PTX was developed, and two substances were chosen as carrier materials: 1) Polyethylene glycol–polylactic acid (PEG-PLA), the original vehicle of Genexol-PM. 2) Vitamin E-TPGS, an inhibitor of P-glycoprotein (P-gp). P-gp has been proven to be the main cause of MDR. In vitro evaluation indicated that the mixed micelle was an ideal PTX delivery system for the treatment of MDR tumors; the mixed micelle also showed a significantly better drug-loading coefficient than Genexol-PM. 相似文献
145.
Fei Li Chun Song Bian Jian Fei Xu Wan fu Pang Jie Liu Shao Guang Duan Zun-Guo Lei Palta Jiwan Li-Ping Jin 《PloS one》2015,10(3)
Stearoyl-acyl carrier protein desaturase (SAD), locating in the plastid stroma, is an important fatty acid biosynthetic enzyme in higher plants. SAD catalyzes desaturation of stearoyl-ACP to oleyl-ACP and plays a key role in determining the homeostasis between saturated fatty acids and unsaturated fatty acids, which is an important player in cold acclimation in plants. Here, four new full-length cDNA of SADs (ScoSAD, SaSAD, ScaSAD and StSAD) were cloned from four Solanum species, Solanum commersonii, S. acaule, S. cardiophyllum and S. tuberosum, respectively. The ORF of the four SADs were 1182 bp in length, encoding 393 amino acids. A sequence alignment indicated 13 amino acids varied among the SADs of three wild species. Further analysis showed that the freezing tolerance and cold acclimation capacity of S. commersonii are similar to S. acaule and their SAD amino acid sequences were identical but differed from that of S. cardiophyllum, which is sensitive to freezing. Furthermore, the sequence alignments between StSAD and ScoSAD indicated that only 7 different amino acids at residues were found in SAD of S. tuberosum (Zhongshu8) against the protein sequence of ScoSAD. A phylogenetic analysis showed the three wild potato species had the closest genetic relationship with the SAD of S. lycopersicum and Nicotiana tomentosiformis but not S. tuberosum. The SAD gene from S. commersonii (ScoSAD) was cloned into multiple sites of the pBI121 plant binary vector and transformed into the cultivated potato variety Zhongshu 8. A freeze tolerance analysis showed overexpression of the ScoSAD gene in transgenic plants significantly enhanced freeze tolerance in cv. Zhongshu 8 and increased their linoleic acid content, suggesting that linoleic acid likely plays a key role in improving freeze tolerance in potato plants. This study provided some new insights into how SAD regulates in the freezing tolerance and cold acclimation in potato. 相似文献
146.
Biqi Wang Wenjing Gao Canqing Yu Weihua Cao Jun Lv Shengfeng Wang Zengchang Pang Liming Cong Hua Wang Xianping Wu Liming Li 《PloS one》2015,10(4)
Previous studies have shown that both single nucleotide polymorphisms (SNPs) and questionnaires-based method can be used for twin zygosity determination, but few validation studies have been conducted using Chinese populations. In the current study, we recruited 192 same sex Chinese adult twin pairs to evaluate the validity of using genetic markers-based method and questionnaire-based method in zygosity determination. We considered the relatedness analysis based on more than 0.6 million SNPs genotyping as the golden standards for zygosity determination. After quality control, qualified twins were left for relatedness analysis based on identical by descent calculation. Then those same sex twin pairs were included in the zygosity questionnaire validation analysis. Logistic regression model was applied to assess the discriminant ability of age, sex and the three questions in zygosity determination. Leave one out cross-validation was used as a measurement of internal validation. The results of zygosity determination based on 65 SNPs in 450k methylation array were all consistent with genotyping. Age, gender, questions of appearance confused by strangers and previously perceived zygosity consisted of the most predictable model with a consistency rate of 0.8698, cross validation predictive error of 0.1347. For twin studies with genotyping and\or 450k methylation array, there would be no need to conduct other zygosity testing for the sake of costs consideration. 相似文献
147.
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
148.
Cheuk-Chun Szeto Bonnie Ching-Ha Kwan Kai-Ming Chow Jeffrey Sung-Shing Kwok Ka-Bik Lai Phyllis Mei-Shan Cheng Wing-Fai Pang Jack Kit-Chung Ng Michael Ho-Ming Chan Lydia Choi-Wan Lit Chi-Bon Leung Philip Kam-Tao Li 《PloS one》2015,10(5)
BackgroundCirculating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that plasma bacterial DNA level predicts cardiovascular events in new PD patients.MethodsWe measured plasma bacterial DNA level in 191 new PD patients, who were then followed for at least a year for the development of cardiovascular event, hospitalization, and patient survival.ResultsThe average age was 59.3 ± 11.8 years; plasma bacterial DNA level 34.9 ± 1.5 cycles; average follow up 23.2 ± 9.7 months. At 24 months, the event-free survival was 86.1%, 69.8%, 55.4% and 30.8% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (p < 0.0001). After adjusting for confounders, plasma bacterial DNA level, baseline residual renal function and malnutrition-inflammation score were independent predictors of composite cardiovascular end-point; each doubling in plasma bacterial DNA level confers a 26.9% (95% confidence interval, 13.0 – 42.5%) excess in risk. Plasma bacterial DNA also correlated with the number of hospital admission (r = -0.379, p < 0.0001) and duration of hospitalization for cardiovascular reasons (r = -0.386, p < 0.0001). Plasma bacterial DNA level did not correlate with baseline arterial pulse wave velocity (PWV), but with the change in carotid-radial PWV in one year (r = -0.238, p = 0.005).ConclusionsCirculating bacterial DNA fragment level is a strong predictor of cardiovascular event, need of hospitalization, as well as the progressive change in arterial stiffness in new PD patients. 相似文献
149.
Targeted Next-Generation Sequencing in Uyghur Families with Non-Syndromic Sensorineural Hearing Loss
Ying Chen Zhentao Wang Zhaoyan Wang Dongye Chen Yongchuan Chai Xiuhong Pang Lianhua Sun Xiaowen Wang Tao Yang Hao Wu 《PloS one》2015,10(5)
The mutation spectrum of deafness genes may vary in different ethnical groups. In this study, we investigated the genetic etiology of nonsyndromic deafness in four consanguineous and two multiplex Uyghur families in which mutations in common deafness genes GJB2, SLC26A4 and MT-RNR1 were excluded. Targeted next-generation sequencing of 97 deafness genes was performed in the probands of each family. Novel pathogenic mutations were identified in four probands including the p.L416R/p.A438T compound heterozygous mutations in TMC1, the homozygous p.V1880E mutation in MYO7A, c.1238delT frameshifting deletion in PCDH15 and c.9690+1G>A splice site mutation in MYO15A. Co-segregation of the mutations and the deafness were confirmed within each family by Sanger sequencing. No pathogenic mutations were identified in one multiplex family and one consanguineous family. Our study provided a useful piece of information for the genetic etiology of deafness in Uyghurs. 相似文献
150.