全文获取类型
收费全文 | 17100篇 |
免费 | 1460篇 |
国内免费 | 2063篇 |
出版年
2024年 | 60篇 |
2023年 | 264篇 |
2022年 | 563篇 |
2021年 | 931篇 |
2020年 | 667篇 |
2019年 | 805篇 |
2018年 | 833篇 |
2017年 | 580篇 |
2016年 | 749篇 |
2015年 | 1168篇 |
2014年 | 1282篇 |
2013年 | 1319篇 |
2012年 | 1669篇 |
2011年 | 1447篇 |
2010年 | 910篇 |
2009年 | 861篇 |
2008年 | 953篇 |
2007年 | 856篇 |
2006年 | 750篇 |
2005年 | 640篇 |
2004年 | 561篇 |
2003年 | 464篇 |
2002年 | 379篇 |
2001年 | 235篇 |
2000年 | 222篇 |
1999年 | 228篇 |
1998年 | 148篇 |
1997年 | 171篇 |
1996年 | 141篇 |
1995年 | 119篇 |
1994年 | 117篇 |
1993年 | 80篇 |
1992年 | 86篇 |
1991年 | 75篇 |
1990年 | 71篇 |
1989年 | 35篇 |
1988年 | 42篇 |
1987年 | 33篇 |
1986年 | 20篇 |
1985年 | 30篇 |
1984年 | 13篇 |
1983年 | 13篇 |
1982年 | 13篇 |
1980年 | 2篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1965年 | 1篇 |
1950年 | 5篇 |
1911年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 406 毫秒
1.
Tao Tian Danhua Yao Lei Zheng Zhiyuan Zhou Yantao Duan Bin Liu Pengfei Wang Yousheng Li 《Cell death & disease》2020,11(12)
Previously, we confirmed that sphingosine kinase 1 (SphK1) inhibition improves sepsis-associated liver injury. High-mobility group box 1 (HMGB1) translocation participates in the development of acute liver failure. However, little information is available on the association between SphK1 and HMGB1 translocation during sepsis-associated liver injury. In the present study, we aimed to explore the effect of SphK1 inhibition on HMGB1 translocation and the underlying mechanism during sepsis-associated liver injury. Primary Kupffer cells and hepatocytes were isolated from SD rats. The rat model of sepsis-associated liver damage was induced by intraperitoneal injection with lipopolysaccharide (LPS). We confirmed that Kupffer cells were the cells primarily secreting HMGB1 in the liver after LPS stimulation. LPS-mediated HMGB1 expression, intracellular translocation, and acetylation were dramatically decreased by SphK1 inhibition. Nuclear histone deacetyltransferase 4 (HDAC4) translocation and E1A-associated protein p300 (p300) expression regulating the acetylation of HMGB1 were also suppressed by SphK1 inhibition. HDAC4 intracellular translocation has been reported to be controlled by the phosphorylation of HDAC4. The phosphorylation of HDAC4 is modulated by CaMKII-δ. However, these changes were completely blocked by SphK1 inhibition. Additionally, by performing coimmunoprecipitation and pull-down assays, we revealed that SphK1 can directly interact with CaMKII-δ. The colocalization of SphK1 and CaMKII-δ was verified in human liver tissues with sepsis-associated liver injury. In conclusion, SphK1 inhibition diminishes HMGB1 intracellular translocation in sepsis-associated liver injury. The mechanism is associated with the direct interaction of SphK1 and CaMKII-δ.Subject terms: Hepatotoxicity, Sepsis 相似文献
2.
Jin Wei Mia Madel Alfajaro Peter C. DeWeirdt Ruth E. Hanna William J. Lu-Culligan Wesley L. Cai Madison S. Strine Shang-Min Zhang Vincent R. Graziano Cameron O. Schmitz Jennifer S. Chen Madeleine C. Mankowski Renata B. Filler Neal G. Ravindra Victor Gasque Fernando J. de Miguel Ajinkya Patil Huacui Chen Craig B. Wilen 《Cell》2021,184(1):76-91.e13
- Download : Download high-res image (212KB)
- Download : Download full-size image
3.
Many animals exhibit different behaviors in different seasons. The photoperiod can have effects on migration, breeding, fur growth, and other processes. The cyclic growth of the fur and feathers of some species of mammals and birds, respectively, is stimulated by the photoperiod as a result of hormone-dependent regulation of the nervous system. To further examine this phenomenon, we evaluated the Arbas Cashmere goat (Capra hircus), a species that is often used in this type of research. The goats were exposed to an experimentally controlled short photoperiod to study the regulation of cyclic cashmere growth. Exposure to a short photoperiod extended the anagen phase of the Cashmere goat hair follicle to increase cashmere production. Assessments of tissue sections indicated that the short photoperiod significantly induced cashmere growth. This conclusion was supported by a comparison of the differences in gene expression between the short photoperiod and natural conditions using gene chip technology. Using the gene chip data, we identified genes that showed altered expression under the short photoperiod compared to natural conditions, and these genes were found to be involved in the biological processes of hair follicle growth, structural composition of the hair follicle, and the morphogenesis of the surrounding skin appendages. Knowledge about differences in the expression of these genes as well as their functions and periodic regulation patterns increases our understanding of Cashmere goat hair follicle growth. This study also provides preliminary data that may be useful for the development of an artificial method to improve cashmere production by controlling the light cycle, which has practical significance for livestock breeding. 相似文献
4.
5.
Hailong Jin Congran Li Ding Li Ming Cai Zhouli Li Shuang Wang Xin Hong Bingyi Shi 《Cell biochemistry and biophysics》2013,67(3):1067-1074
Immunotoxins with selective cytotoxicity are frequently used as therapeutic immunosuppressive agents in solid-organ transplantation because of their efficiency and high specificity. In this study, we present a new recombinant immunotoxin termed anti-CTLA-4-scFv–melittin prepared from Escherichia coli aimed at clearing activated T cells at the same time avoiding all-round decline in systematic immunity. This fusion protein is composed of anti-CTLA-4-scFv unit and melittin analog unit with properties of low immunogenicity and selective cytotoxicity to CTLA-4-positive T cells. In preliminary biological activity assays, our results confirmed the feasibility of activated T cell clearance strategy and there were significant differences in cell survival rates between CTLA-4-positive group and control group at all experimental concentrations of the immunotoxin. The selective cytotoxicity, low immunogenicity, and low production cost make it an attractive alternate to traditional immunosuppressants. 相似文献
6.
Metabolic pathway analysis, one of the most important fields in biochemistry, is pivotal to understanding the maintenance and modulation of the functions of an organism. Good comprehension of metabolic pathways is critical to understanding the mechanisms of some fundamental biological processes. Given a small molecule or an enzyme, how may one identify the metabolic pathways in which it may participate? Answering such a question is a first important step in understanding a metabolic pathway system. By utilizing the information provided by chemical-chemical interactions, chemical-protein interactions, and protein-protein interactions, a novel method was proposed by which to allocate small molecules and enzymes to 11 major classes of metabolic pathways. A benchmark dataset consisting of 3,348 small molecules and 654 enzymes of yeast was constructed to test the method. It was observed that the first order prediction accuracy evaluated by the jackknife test was 79.56% in identifying the small molecules and enzymes in a benchmark dataset. Our method may become a useful vehicle in predicting the metabolic pathways of small molecules and enzymes, providing a basis for some further analysis of the pathway systems. 相似文献
7.
8.
Novel 2D van der Waals heterostructures with innovative bimetallic oxychloride (Bi‐ and Sb‐based oxychloride) nanosheets that are well dispersed on reduced graphene oxide nanosheets, are established through element engineering for superior potassium ion battery (PIBs) anodes. This material displays an exceptional electrochemical performance, obtaining a discharge capacity as high as 360 mAh g?1 at 100 mA g?1 after running 1000 cycles for over 9 months with a capacity preservation percentage of 88.5% and achieving a discharge capacity as high as 319 mAh g?1 at 1000 mA g?1, in addition to the low charge/discharge plateaus for anodes and promising full cell performance. More significantly, the nature of such 2D van der Waals heterostructures, including the element engineering for morphology control, the function of each component of heterostructures, the mechanism of potassium ion storage, and the process of K+ intercalation accompanied with the lattice distortion and chemical bond breakages, is explored in depth. This study is critical for not only paving the way for the practical application of PIBs but also shedding light on fundamentals of potassium ion storage in 2D van der Waals heterostructures. 相似文献
9.
The effects of dispersal limitation and topographic heterogeneity on beta diversity and phylobetadiversity in a subtropical forest 总被引:1,自引:0,他引:1
Yue Bin Zhigao Wang Zhangming Wang Wanhui Ye Honglin Cao Juyu Lian 《Plant Ecology》2010,209(2):237-256
We assessed the effects of topographic heterogeneity and stem density on species composition between grains of different sizes
(20 × 20, 50 × 50, and 100 × 100 m), based on partial Mantel tests. Similarity in species composition was measured by the
abundance-based Jaccard index (C_J) and by an index that incorporates phylogenetic information into C_J (pC_J). Plants were
divided into five groups, arbor, subarbor, and shrub according to life form and two other groups: species that produce dry
fruits (PDF) and that produce fleshy fruits (PFF). C_J and pC_J between any two grains at each grain size were calculated
separately for these groups and for all species combined. In order to examine what influences C_J and pC_J, we analyzed their
correlations with topographic heterogeneity variables and two dispersal limitation-related variables (stem and topographic
resistance). Our data indicate that at all three grain sizes, C_J and pC_J decrease with increasing distance for all plant
groups. Dispersal limitation and topographic heterogeneity were both important at 20 × 20 and 50 × 50 m grain sizes for C_J
and pC_J of all plant groups; and at 100 × 100 m grain size, topographic heterogeneity dominates over dispersal limitation
for some plant groups. C_J and pC_J of PDFs are less negatively correlated with stem resistance than those of PFFs. We conclude
that both beta diversity and phylobetadiversity are dependent on plant groups and grain sizes. 相似文献
10.
Xiaoqing Wu Xiaorui Xie Linjuan Su Na Lin Bin Liang Nan Guo Qingquan Chen Liangpu Xu Hailong Huang 《Journal of cellular and molecular medicine》2021,25(18):8929-8935
Pallister-Killian syndrome (PKS) is a rare sporadic genetic disorder usually caused by mosaicism of an extra isochromosome of 12p (i(12p)). This retrospective study analysed the prenatal ultrasound manifestations and molecular and cytogenetic results of five PKS foetuses. Samples of amniotic fluid and/or cord blood, skin biopsy and placenta were collected. Conventional karyotyping and single nucleotide polymorphism array (SNP array) were performed on all the amniotic fluid or cord blood samples. Copy number variants sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were also used for the validation for one foetus. All the five foetuses were from pregnancies with advanced parental age. Two foetuses involved structural abnormalities and one foetus had only soft markers, all of which included increased nuchal translucency. The rest two foetuses had normal ultrasounds in the second trimester, which has rarely been reported before. The karyotype revealed typical i(12p) in four cases and a small supernumerary marker chromosome consisting of 12p and 20p in the remaining one case. The proportion of cells with i(12p) ranged from 0 to 100% in cultural cells, while SNP array results suggested 2−4 copies of 12p. For one foetus, metaphase FISH showed normal results, but the interphase FISH suggested cell lines with two, three and four copies of 12p in the amniotic fluid. Advanced parental age may be an important risk factor for PKS, and there were no typical ultrasound manifestations related to PKS. A combination of karyotype analysis and molecular diagnosis is an effective method for the diagnosis of PKS. 相似文献