全文获取类型
收费全文 | 12359篇 |
免费 | 1239篇 |
国内免费 | 2144篇 |
出版年
2024年 | 58篇 |
2023年 | 250篇 |
2022年 | 512篇 |
2021年 | 779篇 |
2020年 | 605篇 |
2019年 | 742篇 |
2018年 | 640篇 |
2017年 | 416篇 |
2016年 | 600篇 |
2015年 | 899篇 |
2014年 | 1070篇 |
2013年 | 1043篇 |
2012年 | 1279篇 |
2011年 | 1113篇 |
2010年 | 751篇 |
2009年 | 664篇 |
2008年 | 752篇 |
2007年 | 621篇 |
2006年 | 560篇 |
2005年 | 484篇 |
2004年 | 449篇 |
2003年 | 353篇 |
2002年 | 264篇 |
2001年 | 135篇 |
2000年 | 120篇 |
1999年 | 101篇 |
1998年 | 81篇 |
1997年 | 71篇 |
1996年 | 52篇 |
1995年 | 57篇 |
1994年 | 33篇 |
1993年 | 26篇 |
1992年 | 34篇 |
1991年 | 17篇 |
1990年 | 23篇 |
1989年 | 16篇 |
1988年 | 11篇 |
1987年 | 10篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 5篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1966年 | 1篇 |
1950年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 125 毫秒
141.
142.
Bing Zhu Yuanzhen Dong Jie Ma Minwei Chen Sida Ruan Wenjie Zhao Jun Feng 《Journal of peptide science》2020,26(11)
Presently, echinocandins have been recommended as the first‐line drugs for the treatment of invasive candidiasis. However, low oral bioavailability and solubility limit their application. To improve this situation, this study chose amino acid and fatty acid as raw materials to modify the nucleus of echinocandin B. Six N‐acylated analogs were screened from the derivatives that possessed potent antifungal activity and good water solubility. Based on antifungal susceptibility and hemolytic toxicity, compound 5 as the candidate had good antifungal activity and no hemolytic effect. Moreover, compared with anidulafungin, compound 5 showed a comparable fungicidal effect, much higher solubility, and lower toxicity. In conclusion, compound 5 has the potential for further research and development on account of reserved antifungal activity, high solubility, and low toxicity. 相似文献
143.
Jianping Duan Ying Li Jie Du Erzhen Duan Yuyu Lei Shimei Liang Xian Zhang Xin Zhao Yunchao Kan Lunguang Yao Xinfeng Yang Xingtan Zhang Xiangwei Wu 《Molecular ecology resources》2020,20(5):1372-1383
Antheraea pernyi is a semi‐domesticated lepidopteran insect species valuable to the silk industry, human health, and ecological tourism. Owing to its economic influence and developmental properties, it serves as an ideal model for investigating divergence of the Bombycoidea super family. However, studies on the karyotype evolution and functional genomics of A. pernyi are limited by scarce genomic resource. Here, we applied PacBio sequencing and chromosome structure capture technique to assemble the first high‐quality A. pernyi genome from a single male individual. The genome is 720.67 Mb long with 49 chromosomes and a 13.77‐Mb scaffold N50. Approximately 441.75 Mb, accounting for 60.74% of the genome, was identified as repeats. The genome comprises 21,431 protein‐coding genes, 85.22% of which were functionally annotated. Comparative genomics analysis suggested that A. pernyi diverged from its common ancestor with A. yamamai ~30.3 million years ago, and that chromosome fission contributed to the increased chromosome number. The genome assembled in this work will not only facilitate future research on A. pernyi and related species but also help to progress comparative genomics analyses in Lepidoptera. 相似文献
144.
Jun Mi Yang Feng Jie Wen Yiqun Su Lin Xu Tingjian Zu Chang Liu David E. Fisher Xunwei Wu 《Pigment cell & melanoma research》2020,33(1):16-29
Primary melanocytes isolated from skin and expanded in culture have been widely used for laboratory research and clinical applications. The conventional method to isolate primary melanocytes from skin usually requires about 3–4 weeks of culture for melanocytes to grow sufficiently to passage. Considering that melanocytes comprise only 3%–7% of epidermal cells in normal human skin, it would be extremely helpful to increase the isolation efficiency and shorten the initial culture time to quickly meet various application needs. Here, we report that adding Y‐27632, a Rho kinase inhibitor, into the initial culture medium for 2 days can dramatically increase the yield of melanocytes. We found that Y‐27632 can promote keratinocyte attachment and survival in the melanocyte culture system, resulting in not only better recovery, but also increased proliferation of melanocytes by a paracrine signaling pathway. More specifically, Y‐27632 significantly induced keratinocyte expression of stem cell factor, which played an important role in enhancing the growth of melanocytes. In summary, Y‐27632 could profoundly enhance the yield of primary melanocytes in the initial culture through paracrine effects on keratinocytes. 相似文献
145.
Jie Dong Jun Lei Nada A. Elsayed Ji Yeon Lee Na Shin Quan Na Anna Chudnovets Bei Jia Xiaohong Wang Irina Burd 《Developmental neurobiology》2020,80(5-6):149-159
Fetuses exposed to an inflammatory environment are predisposed to long‐term adverse neurological outcomes. However, the mechanism by which intrauterine inflammation (IUI) is responsible for abnormal fetal brain development is not fully understood. The mechanistic target of rapamycin (mTOR) signaling pathway is closely associated with fetal brain development. We hypothesized that mTOR signaling might be involved in fetal brain injury and malformation when fetuses are exposed to the IUI environment. A well‐established IUI model was utilized by intrauterine injection of lipopolysaccharide (LPS) to explore the effect of IUI on mTOR signaling in mouse fetal brains. We found that microglia activation in LPS fetal brains was increased, as demonstrated by elevated Iba‐1 protein level and immunofluorescence density. LPS fetal brains also showed reduced neuronal cell counts, decreased cell proliferation demonstrated by low Ki67‐positive density, and elevated neuron apoptosis evidenced by high expression of cleaved Caspase 3. Furthermore, we found that mTOR signaling in LPS fetal brains was elevated at 2 hr after LPS treatment, declined at 6 hr and showed overall inhibition at 24 hr. In summary, our study revealed that LPS‐induced IUI leads to increased activation of microglia cells, neuronal damage, and dynamic alterations in mTOR signaling in the mouse fetal brain. Our findings indicate that abnormal changes in mTOR signaling may underlie the development of future neurological complications in offspring exposed to prenatal IUI. 相似文献
146.
Major depressive disorder takes at least 3 weeks for clinical anti‐depressants, such as serotonin selective reuptake inhibitors, to take effect, and only one‐third of patients remit. Ketamine, a kind of anaesthetic, can alleviate symptoms of major depressive disorder patients in a short time and is reported to be effective to treatment‐resistant depression patients. The rapid and strong anti‐depressant‐like effects of ketamine cause wide concern. In addition to ketamine, caloric restriction and sleep deprivation also elicit similar rapid anti‐depressant‐like effects. However, mechanisms about the rapid anti‐depressant‐like effects remain unclear. Elucidating the mechanisms of rapid anti‐depressant effects is the key to finding new therapeutic targets and developing therapeutic patterns. Therefore, in this review we summarize potential molecular and cellular mechanisms of rapid anti‐depressant‐like effects based on the pre‐clinical and clinical evidence, trying to provide new insight into future therapy. 相似文献
147.
148.
149.
Qundan Lv Jie Qiu Jie Liu Zheng Li Wenting Zhang Qin Wang Jie Fang Junjie Pan Zhengdao Chen Wenliang Cheng Michael S. Barker Xuehui Huang Xin Wei Kejun Cheng 《The Plant journal : for cell and molecular biology》2020,103(5):1910-1923
Chimonanthus salicifolius, a member of the Calycanthaceae of magnoliids, is one of the most famous medicinal plants in Eastern China. Here, we report a chromosome‐level genome assembly of C. salicifolius, comprising 820.1 Mb of genomic sequence with a contig N50 of 2.3 Mb and containing 36 651 annotated protein‐coding genes. Phylogenetic analyses revealed that magnoliids were sister to the eudicots. Two rounds of ancient whole‐genome duplication were inferred in the C. salicifolious genome. One is shared by Calycanthaceae after its divergence with Lauraceae, and the other is in the ancestry of Magnoliales and Laurales. Notably, long genes with > 20 kb in length were much more prevalent in the magnoliid genomes compared with other angiosperms, which could be caused by the length expansion of introns inserted by transposon elements. Homologous genes within the flavonoid pathway for C. salicifolius were identified, and correlation of the gene expression and the contents of flavonoid metabolites revealed potential critical genes involved in flavonoids biosynthesis. This study not only provides an additional whole‐genome sequence from the magnoliids, but also opens the door to functional genomic research and molecular breeding of C. salicifolius. 相似文献
150.
Enhui Shen Tianzi Chen Xintian Zhu Longjiang Fan Jie Sun Danny J. Llewellyn Iain Wilson Qian‐Hao Zhu 《The Plant journal : for cell and molecular biology》2020,103(6):2084-2099
Some plant microRNA (miRNA) families contain multiple members generating identical or highly similar mature miRNA variants. Mechanisms underlying the expansion of miRNA families remain elusive, although tandem and/or segmental duplications have been proposed. In this study of two tetraploid cottons, Gossypium hirsutum and Gossypium barbadense, and their extant diploid progenitors, Gossypium arboreum and Gossypium raimondii, we investigated the gain and loss of members of the miR482/2118 superfamily, which modulates the expression of nucleotide‐binding site leucine‐rich repeat (NBS‐LRR) disease resistance genes. We found significant expansion of MIR482/2118d in G. barbadense, G. hirsutum and G. raimondii, but not in G. arboreum. Several newly expanded MIR482/2118d loci have mutated to produce different miR482/2118 variants with altered target‐gene specificity. Based on detailed analysis of sequences flanking these MIR482/2118 loci, we found that this expansion of MIR482/2118d and its derivatives resulted from an initial capture of an MIR482/2118d by a class‐II DNA transposable element (TE) in G. raimondii prior to the tetraploidization event, followed by transposition to new genomic locations in G. barbadense, G. hirsutum and G. raimondii. The ‘GosTE’ involved in the capture and proliferation of MIR482/2118d and its derivatives belongs to the PIF/Harbinger superfamily, generating a 3‐bp target site duplication upon insertion at new locations. All orthologous MIR482/2118 loci in the two diploids were retained in the two tetraploids, but mutation(s) in miR482/2118 were observed across all four species as well as in different cultivars of both G. barbadense and G. hirsutum, suggesting a dynamic co‐evolution of miR482/2118 and its NBS‐LRR targets. Our results provide fresh insights into the mechanisms contributing to MIRNA proliferation and enrich our knowledge on TEs. 相似文献