全文获取类型
收费全文 | 4450篇 |
免费 | 382篇 |
国内免费 | 277篇 |
专业分类
5109篇 |
出版年
2024年 | 11篇 |
2023年 | 46篇 |
2022年 | 136篇 |
2021年 | 233篇 |
2020年 | 169篇 |
2019年 | 187篇 |
2018年 | 201篇 |
2017年 | 133篇 |
2016年 | 183篇 |
2015年 | 292篇 |
2014年 | 356篇 |
2013年 | 333篇 |
2012年 | 416篇 |
2011年 | 353篇 |
2010年 | 210篇 |
2009年 | 223篇 |
2008年 | 252篇 |
2007年 | 198篇 |
2006年 | 166篇 |
2005年 | 135篇 |
2004年 | 110篇 |
2003年 | 119篇 |
2002年 | 113篇 |
2001年 | 80篇 |
2000年 | 72篇 |
1999年 | 53篇 |
1998年 | 28篇 |
1997年 | 35篇 |
1996年 | 37篇 |
1995年 | 44篇 |
1994年 | 33篇 |
1993年 | 24篇 |
1992年 | 27篇 |
1991年 | 22篇 |
1990年 | 17篇 |
1989年 | 14篇 |
1988年 | 8篇 |
1987年 | 8篇 |
1986年 | 9篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有5109条查询结果,搜索用时 15 毫秒
61.
62.
Juan Yi Guang Lu Li Li Xiaozhen Wang Li Cao Ming Lin Sha Zhang Genze Shao 《Nucleic acids research》2015,43(9):4579-4590
The E3 ubiquitin ligase HUWE1/Mule/ARF-BP1 plays an important role in integrating/coordinating diverse cellular processes such as DNA damage repair and apoptosis. A previous study has shown that HUWE1 is required for the early step of DNA damage-induced apoptosis, by targeting MCL-1 for proteasomal degradation. However, HUWE1 is subsequently inactivated, promoting cell survival and the subsequent DNA damage repair process. The mechanism underlying its regulation during this process remains largely undefined. Here, we show that the Cullin4B-RING E3 ligase (CRL4B) is required for proteasomal degradation of HUWE1 in response to DNA damage. CUL4B is activated in a NEDD8-dependent manner, and ubiquitinates HUWE1 in vitro and in vivo. The depletion of CUL4B stabilizes HUWE1, which in turn accelerates the degradation of MCL-1, leading to increased induction of apoptosis. Accordingly, cells deficient in CUL4B showed increased sensitivity to DNA damage reagents. More importantly, upon CUL4B depletion, these phenotypes can be rescued through simultaneous depletion of HUWE1, consistent with the role of CUL4B in regulating HUWE1. Collectively, these results identify CRL4B as an essential E3 ligase in targeting the proteasomal degradation of HUWE1 in response to DNA damage, and provide a potential strategy for cancer therapy by targeting HUWE1 and the CUL4B E3 ligase. 相似文献
63.
高等植物性别分化研究的某些进展 总被引:8,自引:1,他引:8
高等植物性别分化研究的某些进展邵宏波(四平师范学院生物工程研究室吉林四平136000)关键词高等植物,性别分化,基因表达SOMEADVANCESINTHESEXUALDIFFERENTIATIONRESEARCHOFHIGHERPLANTS¥Shao... 相似文献
64.
红毛五加叶的三萜皂甙 总被引:2,自引:0,他引:2
红毛五加(AcanthopanaxgiraldiiHarms)系五加科五加属植物,分布于河北、河南、四川、陕西、甘肃等省,有祛风湿、通关节、强筋骨、治痿痹等功效[1]。其化学成分未见报道。本文报道红毛五加叶的5个三萜皂甙(甙Ⅰ、Ⅱ、Ⅲ、Ⅳ和Ⅴ)的分离鉴定。它们均首次从该属植物发现,其结构如下: R1 R2 Ⅰ rham-(1→2)-ara H Ⅱ H rham-(1→4)-glc-(1→6)-glc … 相似文献
65.
Steven Habbous Karen P. Chu Xin Qiu Anthony La Delfa Luke T.G. Harland Ehab Fadhel Angela Hui Bayardo Perez-Ordonez Ilan Weinreb Fei-Fei Liu John Waldron Brian O'Sullivan David Goldstein Wei Xu Shao Hui Huang Geoffrey Liu 《Cancer epidemiology》2013,37(6):820-829
Introduction Human papillomavirus (HPV) is a risk and prognostic factor for oropharyngeal cancer (OPC). Determining whether the incidence of HPV-associated OPC is rising informs health policy. Methods HPV status was ascribed using p16 immunohistochemistry in 683/1474 OPC patients identified from the Princess Margaret Hospital's Cancer Registry (from 2000 to 2010). Missing p16 data was estimated using multiple (n = 100) imputation (MI) and validated using an independent OPC cohort (n = 214). Non-OPC head and neck squamous cell carcinoma (HNSCC) (n = 3262) were also used for time-trend comparison. Regression was used to compare HNSCC subsets and time-trends. The c-index was used to measure the predictive ability of MI. Results The incidence of OPC rose from 23.3% of all HNSCC in 2000 to 31.2% in 2010 (p = 0.002). In the subset of OPC tested for p16, there was no change in p16 positivity over time (p = 0.9). However, p16 testing became more frequent over time (p < 0.0001), but was nonetheless biased, favouring never-smokers [OR 1.87 (95% CI 1.29–2.70)] and tumors of the tonsil [OR 2.30 (1.52–3.47)] or base-of-tongue [OR 1.72 (1.10–2.70)]. These same factors were also associated with p16-positivity [ORs 3.22 (1.27–8.16), 7.26 (3.50–15.1), 5.83 (2.70–12.7), respectively]. Following MI and normalization, the proportion of OPC that was p16-associated rose from 39.8% in 2000 to 65.0% in 2010, p = 0.002, fully explaining the rise in OPC in our patient population. Conclusion The rise in HNSCC referrals seen from 2000 to 2010 at our institution was driven primarily by p16-associated OPC. MI was necessary to derive reliable conclusions when cases with missing data are considerable. 相似文献
66.
Zhou Xin Yang Zhi-Bo Han Yue Ru Ji You Wei Wang Lu Liang Ying Chi Shao Guang Yang Li Na Li Wei Feng Luo Jian Ping Li Dan Dan Chen Wen Jing Du Xiao Cang Cao Guang Sheng Zhuo Tao Wang Zhong Chao Han 《PloS one》2013,8(3)
Mesenchymal stem cells (MSCs) reside in almost all of the body tissues, where they undergo self-renewal and multi-lineage differentiation. MSCs derived from different tissues share many similarities but also show some differences in term of biological properties. We aim to search for significant differences among various sources of MSCs and to explore their implications in physiopathology and clinical translation. We compared the phenotype and biological properties among different MSCs isolated from human term placental chorionic villi (CV), umbilical cord (UC), adult bone marrow (BM) and adipose (AD). We found that CD106 (VCAM-1) was expressed highest on the CV-MSCs, moderately on BM-MSCs, lightly on UC-MSCs and absent on AD-MSCs. CV-MSCs also showed unique immune-associated gene expression and immunomodulation. We thus separated CD106+cells and CD106−cells from CV-MSCs and compared their biological activities. Both two subpopulations were capable of osteogenic and adipogenic differentiation while CD106+CV-MSCs were more effective to modulate T helper subsets but possessed decreased colony formation capacity. In addition, CD106+CV-MSCs expressed more cytokines than CD106−CV-MSCs. These data demonstrate that CD106 identifies a subpopulation of CV-MSCs with unique immunoregulatory activity and reveal a previously unrecognized mechanism underlying immunomodulation of MSCs. 相似文献
67.
Continuous-time Markov processes are often used to model the complex natural phenomenon of sequence evolution. To make the process of sequence evolution tractable, simplifying assumptions are often made about the sequence properties and the underlying process. The validity of one such assumption, time-homogeneity, has never been explored. Violations of this assumption can be found by identifying non-embeddability. A process is non-embeddable if it can not be embedded in a continuous time-homogeneous Markov process. In this study, non-embeddability was demonstrated to exist when modelling sequence evolution with Markov models. Evidence of non-embeddability was found primarily at the third codon position, possibly resulting from changes in mutation rate over time. Outgroup edges and those with a deeper time depth were found to have an increased probability of the underlying process being non-embeddable. Overall, low levels of non-embeddability were detected when examining individual edges of triads across a diverse set of alignments. Subsequent phylogenetic reconstruction analyses demonstrated that non-embeddability could impact on the correct prediction of phylogenies, but at extremely low levels. Despite the existence of non-embeddability, there is minimal evidence of violations of the local time homogeneity assumption and consequently the impact is likely to be minor. 相似文献
68.
Li Hui Wu Xiao Ting Shao Jun Xia Guo Hui Sun Qi Chen Jing Pan Qian Qian Cai Yi Wei Dong Zhong Yi Chen Xiao Mei Yan Min Peng Nanbert Zhong Xing Zhong Wu 《Glycoconjugate journal》2017,34(1):51-59
Sialic acid modification is a kind of post-translational modification. To investigate the regulation effect of sialic acid on neural differentiation, we used CycloManN propanyl perac (CycloManN pro), a metabolic precursor of sialic acid, to treat PC12 cells. We noted that CycloManN pro indeed robustly promoted global sialylation detected by MAL II lectin blot in PC12 cells. Simultaneously, we interestingly found that the neurite outgrowth of PC12 cells was significantly promoted by the CycloManN pro treatment. The profile analysis of sialylated proteins showed that a protein band at 55KD was greatly enhanced especially in PC12L cells after CycloManN pro treatment. After enrichment with lectin MAL II, the proteins in this band were analyzed by mass spectrometry. The results showed that 23 proteins were in the band, but the score of vimentin was the highest among them. To investigate further the role of vimentin in the process of neurite differentiation, vimentin construct was transfected into PC12 cells. We interestingly observed that ectopic expression of vimentin significantly enhanced the neurite outgrowth induced by CycloManN pro. However, after three potential glycosylation sites (Ser-7, Thr-33, Ser-34:) of vimentin were mutated to alanine, overexpression of the mutated vimentin completely lost the enhancement activity for the neural differentiation even in the presence of CycloManN pro. Taken together, our study demonstrated that vimentin was important in the induction of neural differentiation by CycloManN pro. 相似文献
69.
Morphological and ultrastructural characterization of the alimentary canal in larvae of Streltzoviella insularis (Staudinger) (Lepidoptera: Cossidae) 下载免费PDF全文
Streltzoviella insularis (Staudinger) is an important tree‐boring pest, that primarily damages Sophora japonica (Linnaeus) and Ginkgo biloba (Linnaeus), as well as other common species, at great economic cost to the urban landscape construction industry in China. In the present study, the alimentary canal morphology of S. insularis was observed using light microscopy, and its ultrastructure was investigated by scanning and transmission electron microscopy. The foregut of S. insularis can be divided into the pharynx, esophagus, crop, proventriculus, and cardiac valve. The well‐developed crop forms the longest section of the foregut. It is able to store large amounts of food and is lined with a monolayer of epithelial cells. Many sclerotized microspines occur on the surface of the anterior intima and there are dense spines on the posterior intima of the proventriculus. Epithelial cells of the midgut include columnar cells, goblet cells, and regenerative cells, but endocrine cells are absent. The hindgut consists of the pyloric valve, ileum, and rectum. There is no clear distinction between the ileum and colon. The intima surface of the pyloric valve carries many microspines, whereas the intestinal wall of the rectum is thin with well‐developed rectal pads. The rectal epithelial cells form a squamous monolayer. A cryptonephric excretory system is located in the hindgut. There are six spiral Malpighian tubules, in which a cellular layer on a basement membrane encloses a lumen. These results will provide the basis for further studies of the structure and function in S. insularis larvae. 相似文献
70.
Norcantharidin (NCTD), a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM), the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN). Moreover, the cells could be killed in a dose-/ time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen) expression, destruction of mitochondrial membrane potential (MMP), down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5‘-monophosphate -activated protein kinase) . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP. 相似文献