全文获取类型
收费全文 | 5367篇 |
免费 | 511篇 |
国内免费 | 208篇 |
出版年
2023年 | 46篇 |
2022年 | 108篇 |
2021年 | 189篇 |
2020年 | 127篇 |
2019年 | 143篇 |
2018年 | 151篇 |
2017年 | 94篇 |
2016年 | 172篇 |
2015年 | 279篇 |
2014年 | 293篇 |
2013年 | 356篇 |
2012年 | 388篇 |
2011年 | 378篇 |
2010年 | 244篇 |
2009年 | 205篇 |
2008年 | 259篇 |
2007年 | 228篇 |
2006年 | 246篇 |
2005年 | 189篇 |
2004年 | 202篇 |
2003年 | 152篇 |
2002年 | 130篇 |
2001年 | 109篇 |
2000年 | 108篇 |
1999年 | 99篇 |
1998年 | 44篇 |
1997年 | 45篇 |
1996年 | 38篇 |
1995年 | 36篇 |
1994年 | 43篇 |
1993年 | 41篇 |
1992年 | 66篇 |
1991年 | 74篇 |
1990年 | 47篇 |
1989年 | 59篇 |
1988年 | 57篇 |
1987年 | 56篇 |
1986年 | 48篇 |
1985年 | 56篇 |
1984年 | 43篇 |
1983年 | 31篇 |
1982年 | 23篇 |
1981年 | 20篇 |
1979年 | 31篇 |
1978年 | 23篇 |
1977年 | 20篇 |
1975年 | 21篇 |
1974年 | 22篇 |
1973年 | 25篇 |
1971年 | 17篇 |
排序方式: 共有6086条查询结果,搜索用时 15 毫秒
991.
992.
Induction of autophagy by an oleanolic acid derivative,SZC017, promotes ROS‐dependent apoptosis through Akt and JAK2/STAT3 signaling pathway in human lung cancer cells
下载免费PDF全文
![点击此处可从《Cell biology international》网站下载免费的PDF全文](/ch/ext_images/free.gif)
993.
In this paper, we present a peculiar metal-dielectric-metal (MDM) nanosandwich grating structure that can achieve extraordinary optical transmission performances at normal incidence in the ultraviolet-visible-near infrared (UV-VIS-NIR) regions. The proposed structure shows three obvious spectrum characteristics: it can obtain high transmittance up to 80 % in NUV region and efficiently blocking visible wavelengths for transverse-magnetic (TM) polarized incidence; a broadband NIR polarizer can be inspired in the wavelength range from 950 to 1400 nm; more surprisingly, these performances do not deteriorated until 30° tilting angle. Compared to other grating structures with single metal overlayer, it shows wider band-stop characteristics and higher broadband transmission transmittance and extinction ratio (ER) in the investigated wavebands. We analyze the underlying physical mechanism by using numerical simulation, which is primarily attributed to metal ultraviolet transparency, surface plasmon polariton (SPP) at metal/dielectric interface, Fabry–Perot (FP)-like cavity mode within this dielectric grating, and optical magnetic resonance especially in the dielectric interlayer of the MDM sandwiched structure. This structure is very important for developing high-performance subwavelength multifunctional integrated optical devices. 相似文献
994.
Lorraine Pelosof Sashidhar Yerram Todd Armstrong Nina Chu Ludmila Danilova Breann Yanagisawa 《Epigenetics》2017,12(7):540-550
Epigenetic control of gene expression is a major determinant of tumor phenotype and has been found to influence sensitivity to individual chemotherapeutic agents. Glutathione peroxidase 3 (GPX3, plasma glutathione peroxidase) is a key component of cellular antioxidant regulation and its gene has been reported to be methylated in specific tumor types. GPX3 role in oxidative damage has been associated with sensitivity to platinums in other tumors but its importance in colorectal cancer (CRC) has not been determined. We examined the role of GPX3 methylation in colorectal carcinoma in determining sensitivity to platinum drugs using primary tumor specimens, cell lines, knockdown cell lines, and tumor cell line xenografts. We find GPX3 promoter region methylation in approximately one third of CRC samples and GPX3 methylation leads to reduced GPX3 expression and increased oxaliplatin and cisplatin sensitivity. In contrast, in cell lines with high baseline levels of GPX3 expression or with the ability to increase GPX3 expression, platinum resistance is increased. The cisplatin IC50 in GPX3-methylated cell lines is approximately 6-fold lower than that in GPX3-unmethylated lines. Additionally, knockdown cell lines with essentially no GPX3 expression require N-acetylcysteine to survive in culture underscoring the importance of GPX3 in redox biology. In vivo, GPX3 methylation predicts tumor xenograft sensitivity to platinum with regression of GPX3 knockdown xenografts with platinum treatment but continued growth of GPX3 wild type xenografts in the presence of platinum. These studies demonstrate the importance of GPX3 for CRC cells resistance to platinums and the potential utility of GPX3 methylation status as a predictive biomarker for platinum sensitivity in CRC. 相似文献
995.
Bin Guo Xiaorui Shi Zhe Ma Moxuan Ji Chu Tang Fu Wang 《The Journal of biological chemistry》2021,297(2)
Precursor messenger RNA (pre-mRNA) splicing is critical for cell growth and development, and errors in RNA splicing frequently cause cellular dysfunction, abnormal gene expression, and a variety of human diseases. However, there is currently a lack of reliable systems to noninvasively monitor the mRNA splicing efficiency in cells and animals. Here, we described the design of a genetically engineered ratiometric dual luciferase reporter to continuously quantify the changes in mRNA splice variants in vivo. This reporter system is encoded within a single polypeptide but on separate exons, thus generating two distinct luciferase signals derived from spliced and unspliced mRNAs. With this reporter, the two kinds of luciferase in the same individual can minimize the influence of indirect factors on splicing, and the ratio of these two luciferase intensities represents the dynamic splicing efficiency of pre-mRNA. Our study offers a convenient and robust tool for the screening and identification of small molecules or trans-acting factors that affect the efficiency of specific splicing reactions. 相似文献
996.
997.
998.
Soil fungi fill pivotal ecological roles in biogeochemical processes, particularly dominating decomposition of lignin. Little is known, however, about the responses of different fungal groups to climate warming with respect to bacteria. In this study, using barcode pyrosequencing, we showed that short-term (15 months) of field exposure of an alpine meadow to warming (elevated 1 and 2 °C) did not markedly alter the overall soil fungal community structures and α-diversity on Tibetan Plateau, but the average β-diversity dramatically decreased in response to warming. However, soil respiration rates were stimulated in the growing season, which significantly (P?0.001) correlated with soil temperature. Particularly, warming triggered dramatic shifts in the community structure of dominate Ascomycota and rare taxa (relative abundance?0.1 %). In addition, the abundances of specific Basidiomycota-affiliated members significantly increased, while Ascomycota showed a range of responses to warming. Collectively, we conclude that the fungal communities are resistant to short-term warming, though variations are observed in certain species and rare taxa. This report indicates that changes in a relatively small subset of the soil fungal community are sufficient to produce substantial changes in function, such as CO2 efflux rates. 相似文献
999.
Cyclophilin-40 (CyP40) is part of the immunophilin family and is found in Hsp90-containing protein complexes. We were interested in identifying proteins that interact with CyP40. CyP40-interacting proteins in HeLa cells were identified using the tandem affinity purification approach. Adenovirus expressing human CyP40 protein (Ad–CyP40), fused with streptavidin and calmodulin binding peptides at the N terminus, was generated. Proteins were separated on a sodium dodecyl sulfate–polyacrylamide gel electrophoresis gel after tandem affinity purification. Here 10 silver-stained protein bands that were enriched in the Ad–CyP40-infected lysate and the corresponding regions in the control lysate were excised, digested by trypsin, and identified by tandem mass spectrometric analysis. Of 11 interacting proteins that were identified, 4 (RACK1, Ku70, RPS3, and NF45) were expressed in rabbit reticulocyte lysate, bacteria, and MCF-7 cells. We confirmed that these proteins interact with CyP40. We observed that RACK1 suppressed the cobalt chloride-induced, hypoxia response element-dependent luciferase activity in MCF-7 cells but not in MCF-7 stable cells expressing approximately 10% of the cellular CyP40 content. In addition, RACK1 reduced the HIF-1α protein accumulation after cobalt chloride treatment, which was not observed when the CyP40 content was down-regulated. Collectively, we conclude that reduction of the HIF-1α protein by RACK1 is CyP40-mediated. 相似文献
1000.
Sigma receptors are small membrane proteins implicated in a number of pathophysiological conditions, including drug addiction, psychosis, and cancer; thus, small molecule inhibitors of sigma receptors have been proposed as potential pharmacotherapeutics for these diseases. We previously discovered that endogenous monochain N-alkyl sphingolipids, including d-erythro-sphingosine, sphinganine, and N,N-dimethylsphingosine, bind to the sigma-1 receptor at physiologically relevant concentrations [Ramachandran, S., et al. (2009) Eur. J. Pharmacol. 609, 19-26]. Here, we investigated several N-alkylamines of varying chain lengths as sigma receptor ligands. Although the K(I) values for N-alkylamines were found to be in the micromolar range, when N-3-phenylpropyl and N-3-(4-nitrophenyl)propyl derivatives of butylamine (1a and 1b, respectively), heptylamine (2a and 2b, respectively), dodecylamine (3a and 3b, respectively), and octadecylamine (4a and 4b, respectively) were evaluated as sigma receptor ligands, we found that these compounds exhibited nanomolar affinities with both sigma-1 and sigma-2 receptors. A screen of high-affinity ligands 2a, 2b, 3a, and 3b against a variety of other receptors and/or transporters confirmed these four compounds to be highly selective mixed sigma-1 and sigma-2 ligands. Additionally, in HEK-293 cells reconstituted with K(v)1.4 potassium channel and the sigma-1 receptor, these derivatives were able to inhibit the outward current from the channel, consistent with sigma receptor modulation. Finally, cytotoxicity assays showed that 2a, 2b, 3a, and 3b were highly potent against a number of cancer cell lines, demonstrating their potential utility as mixed sigma-1 and sigma-2 receptor anticancer agents. 相似文献