全文获取类型
收费全文 | 783篇 |
免费 | 42篇 |
国内免费 | 1篇 |
出版年
2023年 | 11篇 |
2022年 | 22篇 |
2021年 | 41篇 |
2020年 | 36篇 |
2019年 | 69篇 |
2018年 | 49篇 |
2017年 | 29篇 |
2016年 | 53篇 |
2015年 | 45篇 |
2014年 | 53篇 |
2013年 | 64篇 |
2012年 | 67篇 |
2011年 | 52篇 |
2010年 | 37篇 |
2009年 | 24篇 |
2008年 | 31篇 |
2007年 | 26篇 |
2006年 | 25篇 |
2005年 | 16篇 |
2004年 | 21篇 |
2003年 | 9篇 |
2002年 | 10篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1989年 | 2篇 |
1986年 | 1篇 |
1982年 | 3篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1968年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有826条查询结果,搜索用时 281 毫秒
81.
Naderi N Majidi M Mousavi Z Khoramian Tusi S Mansouri Z Khodagholi F 《Neurochemical research》2012,37(4):778-785
Most of the modulating effects of cannabinoids on pain are through putative cannabinoid CB1 and CB2 receptors. However, the
involvement of other receptors is also suggested. Cannabinoid compounds with analgesic activity such as palmitoylethanolamide
(PEA) show low affinity to CB1 and CB2 receptors, yet selectively activate GPR55 receptors. The objective of the present study
was to evaluate the possible role of spinal CB1 and GPR55 receptors on antinociceptive activity of PEA in formalin test as
well as in the spinal expression of IL1-β in rat. Intrathecal (i.t.) administration of PEA (1, 10 μg) significantly decreased
both pain-related scores in formalin test and IL1-β expression in rat spinal cord. Pretreatment of rats with low doses of
CB1 receptor antagonist/GPR55 receptor agonist AM251 (10, 100 ng; i.t.), did not attenuated the effect of PEA, yet even significantly
increased the effect of PEA on IL1-β expression in rat spinal cord. Interestingly, i.t. administration of low doses of AM251
per se significantly decreased both pain related behavior and spinal IL1-β expression in formalin test. These findings suggest
the possible involvement of receptors other than CB1 receptors in spinal pain pathways, such as GPR55, in pain modulating
activity of cannabinoids. 相似文献
82.
Hashemi M Eskandari-Nasab E Fazaeli A Rezaei H Mashhadi MA Arbabi F Taheri M 《Gene》2012,505(1):176-179
Caspase-8 (CASP8) plays a critical role in regulating apoptosis, and its functional polymorphisms may modify cancer risk. We investigated the possible association between CASP8 -652 6N ins/del (rs3834129) and the risk of breast cancer in a sample of Iranian population. This case-control study was done on 236 breast cancer patients and 203 cancer free healthy female. We designed a rapid and simple bi-directional PCR allele-specific amplification (bi-PASA) for detection of CASP8 -652 6N ins/del polymorphism. The results showed that the CASP8 -652 6N del/dl genotype was inversely associated with breast cancer risk (OR=0.33, 95% CI=0.17-0.65, p=0.001). The frequencies of the del allele in cases and controls were 29.1% and 38.6%, respectively. An inverse association between CASP8 6N del variant and the risk of breast cancer (OR=0.66, 95% CI=0.66-0.87, p=0.002) was found. In conclusion, the result suggests that the CASP8 -652 6N del polymorphism plays a protective role in susceptibility to breast cancer in our population. Further studies in other populations with larger samples are needed to confirm these findings. 相似文献
83.
Pierdonato Bruno Giovanna Gentile Rita ManciniClaudia De Vitis Maria Cristina Esposito Davide Scozzi Mario MastrangeloAlberto Ricci Ibrahim Mohsen Gennaro CilibertoMaurizio Simmaco Salvatore Mariotta 《Biochemical and biophysical research communications》2012,426(3):306-309
Background
CpG island hypermethylation of gene promoters and regulatory regions is a well-known mechanism of epigenetic silencing of tumor suppressors and is directly linked to carcinogenesis. Wilm’s tumor gene (WT1) is a tumor suppressor protein involved in the regulation of human cell growth and differentiation and a modulator of oncogenic K Ras signaling in lung cancer. Changes in the pattern of methylation of the WT1 gene have not yet been studied in detail in human lung cancer. In this study we compared the methylation profile of WT1 gene in samples of neoplastic and non-neoplastic lung tissue taken from the same patients.Methods
DNA was extracted from neoplastic and normal lung tissue obtained from 16 patients with non small cell lung cancer (NSCLC). The methylation status of 29 CpG islands in the 5′ region of WT1 was determined by pyrosequencing. Statistical analysis was carried out by T test and Mann Whitney test.Results
The mean percentage of methylation, considering all CpG islands of WT1 in the neoplastic tissues of the 16 NSCLC patients, was 16.2 ± 3.4, whereas in the normal lung tissue from the same patients it was 5.6 ± 1.7 (p < 0.001). Adenocarcinomas presented higher methylation levels than squamous cell carcinomas (p < 0,001).Conclusions
Methylation of WT1 gene is significantly increased in NSCLC. Both histotype and exposure to cigarette smoke heavily influence the pattern of CpG islands which undergo hypermethylation. 相似文献84.
85.
Simone?RiehlEmail author Marion?Benz Nicholas?J.?Conard Hojjat?Darabi Katleen?Deckers Hassan?Fazeli?Nashli Mohsen?Zeidi-Kulehparcheh 《Vegetation History and Archaeobotany》2012,21(2):95-106
The beginnings of agriculture throughout the Fertile Crescent are still not completely understood, particularly at the eastern end of the Fertile Crescent in the area of modern Iran. Archaeobotanical samples from Epipalaeolithic/PPNA Körtik Tepe in southeastern Turkey and from the Pre-Pottery Neolithic sites of Chogha Golan and East Chia Sabz in south western Iran were studied in order to define the status of cultivation at these sites. Preliminary results show the presence of abundant wild progenitor species of crops at the Iranian sites before 10600 cal. b.p., and very few wild progenitor species at Körtik Tepe dated to 11700–11250 cal. b.p. The Iranian sites also indicate size increase of wild barley grain across a sequence of 400 years through either cultivation or changing moisture conditions. 相似文献
86.
Mahdi Mardanpour M Nasr Esfahany M Behzad T Sedaqatvand R 《Biosensors & bioelectronics》2012,31(1):264-269
The circulating population of peripheral T lymphocytes obtained from a blood sample can provide a large amount of information about an individual's medical status and history. Recent evidence indicates that the detection and functional characterization of antigen-specific T cell subsets within the circulating population may provide a diagnostic indicator of disease and has the potential to predict an individual's response to therapy. In this report, a microarray detection platform that combines grating-coupled surface plasmon resonance imaging (GCSPRI) and grating-coupled surface plasmon coupled emission (SPCE) fluorescence detection modalities were used to detect and characterize CD4(+) T cells. The microspot regions of interest (ROIs) printed on the array consisted of immobilized antibodies or peptide loaded MHC monomers (p/MHC) as T cell capture ligands mixed with additional antibodies as cytokine capture ligands covalently bound to the surface of a corrugated gold sensor chip. Using optimized parameters, an unlabeled influenza peptide reactive T cell clone could be detected at a frequency of 0.1% in a mixed T cell sample using GCSPRI. Additionally, after cell binding was quantified, differential TH1 cytokine secretion patterns from a T cell clone cultured under TH1 or TH2 inducing conditions was detected using an SPCE fluorescence based assay. Differences in the secretion patterns of 3 cytokines, characteristic of the inducing conditions, indicated that differences were a consequence of the functional status of the captured cells. A dual mode GCSPRI/SPCE assay can provide a rapid, high content T cell screening/characterization tool that is useful for diagnosing disease, evaluating vaccination efficacy, or assessing responses to immunotherapeutics. 相似文献
87.
Haber M Platt DE Ashrafian Bonab M Youhanna SC Soria-Hernanz DF Martínez-Cruz B Douaihy B Ghassibe-Sabbagh M Rafatpanah H Ghanbari M Whale J Balanovsky O Wells RS Comas D Tyler-Smith C Zalloua PA;Genographic Consortium 《PloS one》2012,7(3):e34288
Afghanistan has held a strategic position throughout history. It has been inhabited since the Paleolithic and later became a crossroad for expanding civilizations and empires. Afghanistan's location, history, and diverse ethnic groups present a unique opportunity to explore how nations and ethnic groups emerged, and how major cultural evolutions and technological developments in human history have influenced modern population structures. In this study we have analyzed, for the first time, the four major ethnic groups in present-day Afghanistan: Hazara, Pashtun, Tajik, and Uzbek, using 52 binary markers and 19 short tandem repeats on the non-recombinant segment of the Y-chromosome. A total of 204 Afghan samples were investigated along with more than 8,500 samples from surrounding populations important to Afghanistan's history through migrations and conquests, including Iranians, Greeks, Indians, Middle Easterners, East Europeans, and East Asians. Our results suggest that all current Afghans largely share a heritage derived from a common unstructured ancestral population that could have emerged during the Neolithic revolution and the formation of the first farming communities. Our results also indicate that inter-Afghan differentiation started during the Bronze Age, probably driven by the formation of the first civilizations in the region. Later migrations and invasions into the region have been assimilated differentially among the ethnic groups, increasing inter-population genetic differences, and giving the Afghans a unique genetic diversity in Central Asia. 相似文献
88.
In Vitro Insulin Release from Thermosensitive Chitosan Hydrogel 总被引:1,自引:0,他引:1
Recently, great attention has been paid to in situ gel-forming chitosan/glycerol-phosphate (chitosan/Gp) solution due to their good biodegradability and thermosensitivity. This in situ gel-forming system is injectable fluid that can be introduced into the body in a minimally invasive manner prior to solidifying within the desired tissue. At the present study, insulin release from chitosan/Gp solution has been investigated. Insulin in different concentrations was loaded in two formulations of chitosan/Gp solution and in vitro drug release was studied over a period of 3 weeks. Results indicated that the release of insulin from chitosan/Gp gel decreases by increasing in Gp salt and initial insulin concentration. Stability of released insulin was investigated by 8-anilino-1-naphthalenesulfonate probe. Results proved that insulin have been released in its native form. Because of simple preparation and administration, prolonged release of insulin and stability of released insulin, this in situ gel-forming system could be used as a controlled release delivery system for insulin.KEY WORDS: biodegradable, chitosan, controlled release, in situ forming, insulin 相似文献
89.
Pedergnana V Abdel-Hamid M Guergnon J Mohsen A Le Fouler L Theodorou I Mohamed MK Fontanet A Plancoulaine S Abel L 《PloS one》2012,7(6):e38578
Spontaneous clearance of hepatitis C virus (HCV) occurs in ~30% of acute infections. Host genetics play a major role in HCV clearance, with a strong effect of single nucleotide polymorphisms (SNPs) of the IL28B gene already found in different populations, mostly infected with viral genotypes 1 and 3. Egypt has the highest prevalence of HCV infection in the world, which is mostly due to viral genotype 4. We investigated the role of several IL28B SNPs in HCV spontaneous clearance in an Egyptian population. We selected nine SNPs within the IL28B genomic region covering the linkage disequilibrium (LD) block known to be associated with HCV clearance in European populations. These SNPs were genotyped in 261 HCV-infected Egyptian subjects (130 with spontaneous clearance and 131 with chronic infection). The most associated SNPs were rs12979860 (P = 1.6 × 10(-7)) and the non-synonymous IL28B SNP, rs8103142 (P = 1.6 × 10(-7)). Interestingly, three SNPs at the two bounds of the region were monomorphic, reducing the size of the LD block in which the causal variants are potentially located to ~20 kilobases. HCV clearance in Egypt was associated with a region of IL28B smaller than that identified in European populations, and involved the non-synonymous IL28B SNP, rs8103142. 相似文献
90.