全文获取类型
收费全文 | 1330篇 |
免费 | 86篇 |
国内免费 | 1篇 |
出版年
2023年 | 17篇 |
2022年 | 36篇 |
2021年 | 63篇 |
2020年 | 35篇 |
2019年 | 49篇 |
2018年 | 50篇 |
2017年 | 32篇 |
2016年 | 46篇 |
2015年 | 71篇 |
2014年 | 69篇 |
2013年 | 104篇 |
2012年 | 94篇 |
2011年 | 103篇 |
2010年 | 54篇 |
2009年 | 41篇 |
2008年 | 45篇 |
2007年 | 57篇 |
2006年 | 56篇 |
2005年 | 52篇 |
2004年 | 59篇 |
2003年 | 41篇 |
2002年 | 42篇 |
2001年 | 14篇 |
1999年 | 8篇 |
1998年 | 11篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 6篇 |
1993年 | 5篇 |
1992年 | 7篇 |
1990年 | 5篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 10篇 |
1986年 | 8篇 |
1985年 | 4篇 |
1983年 | 7篇 |
1982年 | 5篇 |
1981年 | 9篇 |
1979年 | 7篇 |
1978年 | 11篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1974年 | 6篇 |
1973年 | 6篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1968年 | 5篇 |
排序方式: 共有1417条查询结果,搜索用时 187 毫秒
61.
Wheat and barley are two of the founder crops of the agricultural revolution that took place 10,000 years ago in the Fertile Crescent and both crops remain among the world's most important crops. Domestication of these crops from their wild ancestors required the evolution of traits useful to humans, rather than survival in their natural environment. Of these traits, grain retention and threshability, yield improvement, changes to photoperiod sensitivity and nutritional value are most pronounced between wild and domesticated forms. Knowledge about the geographical origins of these crops and the genes responsible for domestication traits largely pre-dates the era of nextgeneration sequencing, although sequencing will lead to new insights. Molecular markers were initially used to calculate distance(relatedness), genetic diversity and to generate genetic maps which were useful in cloning major domestication genes. Both crops are characterized by large,complex genomes which were long thought to be beyond the scope of whole-genome sequencing. However, advances in sequencing technologies have improved the state of genomic resources for both wheat and barley. The availability of reference genomes for wheat and some of its progenitors,as well as for barley, sets the stage for answering unresolved questions in domestication genomics of wheat and barley. 相似文献
62.
Mohamed A. Dkhil Mona F. Khalil Marwa S.M. Diab Amira A. Bauomy Simeon Santourlidis Esam M. Al-Shaebi Saleh Al-Quraishy 《Saudi Journal of Biological Sciences》2019,26(7):1468-1472
Nanomedicine is one of the most important methods used to treat human diseases including parasitic diseases. Schistosomiasis is a major parasitic disease that affects human health in tropical regions. Whilst Praziquantel is the main classic antischistosomal drug, new drugs are required due to the poor effect of the drug on the parasite juveniles and immature worms, and the emergence of drug resistant strains of Schistosoma. The present study aimed to examine the curative roles of both gold and selenium nanoparticles on jejunal tissues of mice infected with Schistosoma mansoni. Transmission electron microscopy was used for characterization of nanoparticles. Gold nanoparticles of 1 mg/kg mice body weight and selenium nanoparticles 0.5 mg/kg body weight were inoculated separately into mice infected with S. mansoni. The parasite induced a significant decrease in glutathione levels; however, the levels of nitric oxide and malondialdehyde were significantly increased. Additionally, the parasite introduced deteriorations in histological architecture of the jejunal tissue. Treatment of mice with metal nanoparticles reduced the levels of body weight changes, oxidative stress and histological impairment in the jejunal tissue significantly. Therefore, our results revealed the protective role of both selenium and gold nanoparticles against jejunal injury in mice infected with S. mansoni. 相似文献
63.
Jamal S.M. Sabir Abdelfatteh El Omri Noor A. Shaik Babajan Banaganapalli Nahid H. Hajrah Houda Zrelli Leila Arfaoui Zuhier A. Awan Abdulkader M. Shaikh Omar Arif Mohammed Mona G. Alharbi Alawiah M. Alhebshi Robert K. Jansen Muhummadh Khan 《Saudi Journal of Biological Sciences》2019,26(7):1338-1343
Obesity is a multifactorial metabolic disorder characterized by low grade chronic inflammation. Rare and novel mutations in genes which are vital in several key pathways have been reported to alter the energy expenditure which regulates body weight. The TP53 or p53 gene plays a prominent role in regulating various metabolic activities such as glycolysis, lipolysis, and glycogen synthesis. Recent genome-wide association studies reported that tumor suppressor gene p53 variants play a critical role in the predisposition of type 2 diabetes and obesity. Till date, no reports are available from the Arabian population; hence the present study was intended to assess the association between p53 variants with risk of obesity development in the Saudi population. We have selected three p53 polymorphisms, rs1642785 (C > G), and rs9894946 (A > G), and rs1042522 (Pro72Arg; C > G) and assessed their association with obesity risk in the Saudi population. Phenotypic and biochemical parameters were also evaluated to check their association with p53 genotypes and obesity. Genotyping was carried out on 136 obese and 122 normal samples. We observed that there is significantly increased prevalence p52 Pro72Arg (rs1042522) polymorphism in obese persons when compared to controls at GG genotype in overall comparison (OR: 2.169, 95% CI: 1.086-4.334, p = 0.02716). Male obese subjects showed three-fold higher risk at GG genotype (OR: 3.275, 95% CI: 1.230-8.716, p = 0.01560) and two-fold risk at G allele (OR: 1.827, 95% CI: 1.128-2.958, p = 0.01388) of p53 variant Pro72Arg respectively. This variant has also shown significant influence on cholesterol, LDL level, and random insulin levels in obese subjects (p ≤ 0.05). In conclusion, p53 Pro72Arg variant is highly prevalent among obese individuals and may act as a genetic modifier for obesity development among Saudis. 相似文献
64.
Santini Nadia S. Lovelock Catherine E. Hua Quan Zawadzki Atun Mazumder Debashish Mercer Tim R. Muñoz-Rojas Miriam Hardwick Simon A. Madala Bindu Swapna Cornwell William Thomas Torsten Marzinelli Ezequiel M. Adam Paul Paul Swapan Vergés Adriana 《Ecosystems》2019,22(8):1803-1822
Ecosystems - Saltmarshes provide many valuable ecosystem services including storage of a large amount of ‘blue carbon’ within their soils. To date, up to 50% of the world’s... 相似文献
65.
66.
67.
The Caenorhabditis elegans pumilio homolog, puf-9, is required for the 3'UTR-mediated repression of the let-7 microRNA target gene, hbl-1 总被引:1,自引:0,他引:1
The Puf family of RNA-binding proteins directs cell fates by regulating gene expression at the level of translation and RNA stability. Here, we report that the Caenorhabditis elegans pumilio homolog, puf-9, controls the differentiation of epidermal stem cells at the larval-to-adult transition. Genetic analysis reveals that loss-of-function mutations in puf-9 enhance the lethality and heterochronic phenotypes caused by mutations in the let-7 microRNA (miRNA), while suppressing the heterochronic phenotypes of lin-41, a let-7 target and homolog of Drosophila Brat. puf-9 interacts with another known temporal regulator hbl-1, the Caenorhabditis elegans ortholog of hunchback. We present evidence demonstrating that puf-9 is required for the 3'UTR-mediated regulation of hbl-1, in both the hypodermis and the ventral nerve cord. Finally, we show that this regulation is dependent on a region of the hbl-1 3'UTR that contains putative Puf family binding sites as well as binding sites for the let-7 miRNA family, suggesting that puf-9 and let-7 may mediate hypodermal seam cell differentiation by regulating common targets. 相似文献
68.
Hefnawy MM Sultan MA Al-Shehri MM 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,856(1-2):328-336
A sensitive and selective high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of bufuralol enantiomers in plasma and pharmaceutical formulations. Enantiomeric resolution was achieved on a vancomycin macrocyclic antibiotic chiral stationary phase (CSP) known as Chirobiotic V with UV detection set at 254 nm. The polar ionic mobile phase (PIM) consisting of methanol-glacial acetic acid-triethylamine (100:0.015:0.010, v/v/v) has been used at a flow rate of 0.5 ml/min. The method is highly specific where other coformulated compounds did not interfere. The stability of bufuralol enantiomers under different degrees of temperature was also studied. The results showed that the drug is stable for at least 7 days at 70 degrees C. The method was validated for its linearity, accuracy, precision and robustness. An experimental design was used during validation to evaluate method robustness. The calibration curves in plasma were linear over the range of 5-500 ng/ml for each enantiomer with detection limit of 2 ng/ml. The mean relative standard deviation (RSD) of the results of within-day precision and accuracy of the drug were 0.05) between inter- and intra-day studies for each enantiomer which confirmed the reproducibility of the assay method. The mean extraction efficiency for S-(-)- and R-(+)-bufuralol from plasma was in the range 97-102% at 15-400 ng/ml level for each enantiomer. The overall recoveries of bufuralol enantiomers from pharmaceutical formulations was in the range 99.6-102.2% with %RSD ranging from 1.06 to 1.16%. The assay method proved to be suitable as chiral quality control for bufuralol formulations by HPLC and for therapeutic drug monitoring. 相似文献
69.
70.
HER2+ mCRC patients with exon 20 R784G substitution mutation do not respond to the cetuximab therapy
Ehsan Gharib Reza Salmanipour Ehsan Nazemalhosseini Mojarad Mohammad Yaghoob Taleghani Saharnaz Sarlak Mona Malekzade-Moghani Parinaz Nasri Nasrabadi Mohammad Amin Meiary Hamid Asadzadeh Aghdaei Mohammad Reza Zali 《Journal of cellular physiology》2019,234(8):13137-13144
The human epidermal growth factor 2 (HER2) gene undergoes various mutations that could alter its activity or respond to the antibody therapies. Cetuximab, a known anti-EGFR monoclonal antibody (mAB), is widely administered in metastatic colorectal cancer (mCRC) cases. Here we identified mCRC patients who did not respond to cetuximab (500 mg/m2, q2w) after fluoropyrimidine/oxaliplatin regimen failure. Tumor samples were examined with immunohistochemistry for protein distribution, polymerase chain reaction (PCR) sequencing for mutation detection and real-time PCR for mRNA expression pattern analysis between cetuximab sensitive and resistance patients. The conformational differences of normal and mutated protein structures were predicted by bioinformatics analysis. The 5-year survival rates of target groups were estimated using the Kaplan–Meier method. Immunohistochemistry showed that all cases had high level of HER2 protein. No K-Ras or B-Raf mutation was observed among the study population; however, cetuximab resistance patients harbored a somatic mutation R784G at the exon 20 region of HER2 coding sequence. According to bioinformatics analysis, this mutation caused a notable misfold in protein conformation. Meanwhile, survival analysis showed R784G mutated mCRC patients had shortened survival rate compared with the mCRC cases with wild-type HER2. Collectively, these data report a new mechanism of resistance to cetuximab and might be applicable in modifying new therapeutic strategies for HER2 involved cancers. 相似文献