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991.
Evaluation of tubulin β‐3 as a novel senescence‐associated gene in melanocytic malignant transformation
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Kyriakos Orfanidis Petra Wäster Katarzyna Lundmark Inger Rosdahl Karin Öllinger 《Pigment cell & melanoma research》2017,30(2):243-254
Malignant melanoma might develop from melanocytic nevi in which the growth‐arrested state has been broken. We analyzed the gene expression of young and senescent human melanocytes in culture and compared the gene expression data with a dataset from nevi and melanomas. A concordant altered gene expression was identified in 84 genes when comparing the growth‐arrested samples with proliferating samples. TUBB3, which encodes the microtubule protein tubulin β‐3, showed a decreased expression in senescent melanocytes and nevi and was selected for further studies. Depletion of tubulin β‐3 caused accumulation of cells in the G2/M phase and decreased proliferation and migration. Immunohistochemical assessment of tubulin β‐3 in benign lesions revealed strong staining in the superficial part of the intradermal components, which faded with depth. In contrast, primary melanomas exhibited staining without gradient in a disordered pattern and strong staining of the invasive front. Our results describe an approach to find clinically useful diagnostic biomarkers to more precisely identify cutaneous malignant melanoma and present tubulin β‐3 as a candidate marker. 相似文献
992.
Nikki R. Adler Andrew Haydon Catriona A. McLean John W. Kelly Victoria J. Mar 《Pigment cell & melanoma research》2017,30(1):13-27
Metastasis represents the end product of an elaborate biological process, which is determined by a complex interplay between metastatic tumour cells, host factors and homoeostatic mechanisms. Cutaneous melanoma can metastasize haematogenously or lymphogenously. The three predominant models that endeavour to explain the patterns of melanoma progression are the stepwise spread model, the simultaneous spread model and the model of differential spread. The time course to the development of metastases differs between the different metastatic routes. There are several clinical and histopathological risk factors for the different metastatic pathways. In particular, patient sex and the anatomical location of the primary tumour influence patterns of disease progression. There is limited existing evidence regarding the relationship between tumour mutation status, other diagnostic and prognostic biomarkers and the metastatic pathways of primary cutaneous melanoma. This knowledge gap needs to be addressed to better identify patients at high risk of disease recurrence and personalize surveillance strategies. 相似文献
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BackgroundNo previous Australian population-based studies have described or quantified the progression of colorectal cancer (CRC) to metastatic disease. We describe patterns of progression to metastatic disease for an Australian cohort diagnosed with localised or regional CRC.MethodsAll localised and regional CRC cases in the New South Wales Cancer Registry diagnosed during 2000–2007 were followed to December 2011 for subsequent metastases (identified by subsequent disease episode notifications) or CRC death. Cox regression was used to identify factors associated with metastatic progression.ResultsAfter a median 5.3 years follow-up, 26.4% of the 12757 cases initially diagnosed with localised or regional colon cancer had developed metastatic disease, as had 29.5% of the 7154 rectal cancer cases. For both cancer sites, risk of metastatic progression was significantly higher for those initially diagnosed with regional disease (adjusted hazard ratio [aHR] 3.49 for colon, 2.66 for rectal cancer), and for older cases (e.g. aHR for >79 years vs <60 years: 1.38 for colon, 1.69 for rectal cancer). Risk of disease progression was significantly lower for females, and varied by histology type. For colon cancer, the risk of disease progression decreased over time. For rectal cancer, risk of metastatic progression was significantly higher for those living in more socioeconomically disadvantaged areas compared with those in the least disadvantaged area.ConclusionsAn understanding of the variation in risk of metastatic progression is useful for planning health service requirements, and can help inform decisions about treatment and follow-up for colorectal cancer patients. 相似文献
996.
Activating mutations in Gαq/11 are a major driver of uveal melanoma (UM), the most common intraocular cancer in adults. While progress has recently been made in targeting Gαq/11 for UM therapy, the crucial role for these proteins in normal physiology and their high structural similarity with many other important GTPase proteins renders this approach challenging. The aim of the current study was to validate whether a key regulator of Gq signaling, regulator of G protein signaling 2 (RGS2), can inhibit Gαq-mediated UM cell growth. We used two UM cell lines, 92.1 and Mel-202, which both contain the most common activating mutation GαqQ209L and developed stable cell lines with doxycycline-inducible RGS2 protein expression. Using cell viability assays, we showed that RGS2 could inhibit cell growth in both of these UM cell lines. We also found that this effect was independent of the canonical GTPase-activating protein activity of RGS2 but was dependent on the association between RGS2 and Gαq. Furthermore, RGS2 induction resulted in only partial reduction in cell growth as compared to siRNA-mediated Gαq knockdown, perhaps because RGS2 was only able to reduce mitogen-activated protein kinase signaling downstream of phospholipase Cβ, while leaving activation of the Hippo signaling mediators yes-associated protein 1/TAZ, the other major pathway downstream of Gαq, unaffected. Taken together, our data indicate that RGS2 can inhibit UM cancer cell growth by associating with GαqQ209L as a partial effector antagonist. 相似文献
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998.
Kentaro Hayashi Norihiro Itsubo Atsushi Inaba 《The International Journal of Life Cycle Assessment》2000,5(5):265-272
The purpose of our study was to develop damage functions due to ozone layer depletion, that related the emission of ozone
depleting substances (ODS) to the damage of category endpoints. The ozone layer depletion causes many types of damage such
as skin cancer, cataract, adverse effect to crop and plant growth. We assessed the increase of skin cancer incidence risk.
The damage function have been developed with connecting the main processes on ozone depletion, emission of ODS, increase of
tropospheric ODS, increase of stratospheric ODS, change of total ozone, change of B region ultra-violet (UV-B) at the surface,
and the increase of skin cancer incidence. As the result, we could introduce damage functions of melanoma and non-melanoma
skin cancer incidence for 13 species of ODSs and damage factors based on the disability-adjusted life years (DALYs). We also
compared the DALYs value with the damage factors of Eco-indicator 99 (egalitarian and hierarchic value), and it was found
that our result was several ten times as small except methyl bromide. Furthermore, a case study for refrigerator was performed
and it showed that shifting to less ozone depleting substances reduced the risk of skin cancer incidence to one-fourteenth
in DALYs. 相似文献
999.
Jiaoduan Li Jing Long Jianglin Zhang Nian Liu Bei Yan Ling Tang Xiang Chen Cong Peng 《Journal of cellular and molecular medicine》2022,26(9):2579
Melanoma is a fatal cancer with a significant feature of resistance to traditional chemotherapeutic drugs and radiotherapy. A mutation in the kinase BRAF is observed in more than 66% of metastatic melanoma cases. Therefore, there is an urgent need to develop new BRAF‐mutant melanoma inhibitors. High‐dose chloroquine has been reported to have antitumour effects, but it often induces dose‐limiting toxicity. In this study, a series of chloroquine derivatives were synthesized, and lj‐2‐66 had the best activity and was selected for further investigation. Furthermore, the anti‐BRAF‐mutant melanoma effect and mechanism of this compound were explored. CCK‐8 and colony formation assays indicated that lj‐2‐66 significantly inhibited the proliferation of BRAF‐mutant melanoma cells. Flow cytometry revealed that lj‐2‐66 induced G2/M arrest in melanoma cells and promoted apoptosis. Furthermore, lj‐2‐66 increased the level of ROS in melanoma cells and induced DNA damage. Interestingly, lj‐2‐66 also played a similar role in BRAF inhibitor‐resistant melanoma cells. In summary, we found a novel chloroquine derivative, lj‐2‐66, that increased the level of ROS in melanoma cells and induced DNA damage, thus leading to G2/M arrest and apoptosis. These findings indicated that lj‐2‐66 may become a potential therapeutic drug for melanoma harbouring BRAF mutations. 相似文献
1000.
Tongwu Zhang Jiyeon Choi Ramile Dilshat Berglind
sk Einarsdttir Michael A. Kovacs Mai Xu Michael Malasky Salma Chowdhury Kristine Jones D. Timothy Bishop Alisa M. Goldstein Mark M. Iles Maria Teresa Landi Matthew H. Law Jianxin Shi Eiríkur Steingrímsson Kevin M. Brown 《American journal of human genetics》2021,108(9):1631