全文获取类型
收费全文 | 17170篇 |
免费 | 2358篇 |
国内免费 | 606篇 |
出版年
2024年 | 96篇 |
2023年 | 601篇 |
2022年 | 812篇 |
2021年 | 1419篇 |
2020年 | 1357篇 |
2019年 | 1939篇 |
2018年 | 1267篇 |
2017年 | 841篇 |
2016年 | 755篇 |
2015年 | 941篇 |
2014年 | 1473篇 |
2013年 | 1764篇 |
2012年 | 764篇 |
2011年 | 903篇 |
2010年 | 489篇 |
2009年 | 597篇 |
2008年 | 540篇 |
2007年 | 562篇 |
2006年 | 526篇 |
2005年 | 423篇 |
2004年 | 339篇 |
2003年 | 302篇 |
2002年 | 248篇 |
2001年 | 152篇 |
2000年 | 129篇 |
1999年 | 116篇 |
1998年 | 127篇 |
1997年 | 94篇 |
1996年 | 89篇 |
1995年 | 76篇 |
1994年 | 63篇 |
1993年 | 54篇 |
1992年 | 56篇 |
1991年 | 49篇 |
1990年 | 24篇 |
1989年 | 25篇 |
1988年 | 29篇 |
1987年 | 23篇 |
1986年 | 9篇 |
1985年 | 20篇 |
1984年 | 15篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 281 毫秒
221.
222.
Giovanni Corso Joana Figueiredo Simone Pietro De Angelis Federica Corso Antonia Girardi Joana Pereira Raquel Seruca Bernardo Bonanni Patricia Carneiro Gabriella Pravettoni Elena Guerini Rocco Paolo Veronesi Giacomo Montagna Virgilio Sacchini Sara Gandini 《Journal of cellular and molecular medicine》2020,24(11):5930-5936
E-cadherin protein (CDH1 gene) integrity is fundamental to the process of epithelial polarization and differentiation. Deregulation of the E-cadherin function plays a crucial role in breast cancer metastases, with worse prognosis and shorter overall survival. In this narrative review, we describe the inactivating mechanisms underlying CDH1 gene activity and its possible translation to clinical practice as a prognostic biomarker and as a potential targeted therapy. 相似文献
223.
Jingliang Cheng Jiangzhou Peng Jiewen Fu Md. Asaduzzaman Khan Pingping Tan Chunli Wei Xiyun Deng Hanchun Chen Junjiang Fu 《Journal of cellular and molecular medicine》2020,24(2):1676-1683
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer‐related deaths in women worldwide. In this study, a large Chinese pedigree with breast cancer including a proband and two female patients was recruited and a familial history of breast cancer was collected by questionnaire. Clinicopathological assessments and neoadjuvant therapy‐related information were obtained for the proband. Blood samples were taken, and gDNA was extracted. The BRCA1/2 and PALB2 genes were screened using next‐generation sequencing by a targeted gene panel. We have successfully identified a novel, germline heterozygous, missense mutation of the gene BRCA2: c.7007G>T, p.R2336L, which is likely to be pathogenic in the proband and her elder sister who both had breast cancer. Furthermore, the risk factors for developing breast cancer in this family are discussed. Thus, genetic counselling and long‐term follow‐up should be provided for this family of breast cancer patients as well as carriers carrying a germline variant of BRCA2: c.7007G>T (p.R2336L). 相似文献
224.
Xiao Fu Guanghui Cui Shuaishuai Liu Song Zhao 《Journal of cellular and molecular medicine》2020,24(2):1670-1675
This study aimed to explore the underlying mechanism of linc01014 in oesophagus cancer gefitinib resistance. Gefitinib‐resistant oesophagus squamous cell carcinoma (ESCC gefitinibR) cell lines were constructed by using different gefitinib treatment in FLO‐1, KYAE‐1, TE‐8 and TE‐5 cell lines and confirmed by MTS50 and proliferation assays. Expression of linc01014 was overexpressed/silenced in FLO‐1 cells followed by gefitinib treatment, and then, the apoptosis‐associated markers Bax and Bcl‐2, and PI3KCA in PI3K signalling pathway were determined using Western blotting. MST50 and morphology analyses showed that ESCC gefitinibR cell lines presented obvious gefitinib resistance than their parental ESCC cell lines. ESCC gefitinibR cell lines showed significantly higher proliferation abilities than their parental ESCC cell lines after treating with gefitinib. Overexpression of linc01014 significantly inhibited the apoptosis of FLO‐1 cells induced by gefitinib and silencing linc01014 obviously promoted the apoptosis of FLO‐1 cells induced by gefitinib. Silencing linc01014 could significantly increase the gefitinib chemotherapy sensitivity of oesophagus cancer via PI3K‐AKT‐mTOR signalling pathway. 相似文献
225.
Liangjun Li Lin Lin Ming Li Weiling Li 《Journal of cellular and molecular medicine》2020,24(3):2308-2318
As a highly potent and highly selective oral inhibitor of FLT3/AXL, gilteritinib showed activity against FLT3D835 and FLT3‐ITD mutations in pre‐clinical testing, although its role on colorectal cancer (CRC) cells is not yet fully elucidated. We examined the activity of gilteritinib in suppressing growth of CRC and its enhancing effect on other drugs used in chemotherapy. In this study, we observed that, regardless of p53 status, treatment using gilteritinib induces PUMA in CRC cells via the NF‐κB pathway after inhibition of AKT and activation of glycogen synthase kinase 3β (GSK‐3β). PUMA was observed to be vital for apoptosis in CRC cells through treatment of gilteritinib. Moreover, enhancing induction of PUMA through different pathways could mediate chemosensitization by using gilteritinib. Furthermore, PUMA deficiency revoked the antitumour role of gilteritinib in vivo. Thus, our results indicate that PUMA mediates the antitumour activity of gilteritinib in CRC cells. These observations are critical for the therapeutic role of gilteritinib in CRC. 相似文献
226.
Yao Wu Peng Chen Li Sun Shengtao Yuan Zujue Cheng Ligong Lu Hongzhi Du Meixiao Zhan 《Journal of cellular and molecular medicine》2020,24(17):9495-9506
Sepiapterin reductase, a homodimer composed of two subunits, plays an important role in the biosynthesis of tetrahydrobiopterin. Furthermore, sepiapterin reductase exhibits a wide distribution in different tissues and is associated with many diseases, including brain dysfunction, chronic pain, cardiovascular disease and cancer. With regard to drugs targeting sepiapterin reductase, many compounds have been identified and provide potential methods to treat various diseases. However, the underlying mechanism of sepiapterin reductase in many biological processes is unclear. Therefore, this article summarized the structure, distribution and function of sepiapterin reductase, as well as the relationship between sepiapterin reductase and different diseases, with the aim of finding evidence to guide further studies on the molecular mechanisms and the potential clinical value of sepiapterin reductase. In particular, the different effects induced by the depletion of sepiapterin reductase or the inhibition of the enzyme suggest that the non‐enzymatic activity of sepiapterin reductase could function in certain biological processes, which also provides a possible direction for sepiapterin reductase research. 相似文献
227.
Wei Zhu Yan Si Jun Xu Yu Lin Jing-Zi Wang Mengda Cao Shanwen Sun Qiang Ding Lingjun Zhu Ji-Fu Wei 《Journal of cellular and molecular medicine》2020,24(6):3521-3533
m6A modification is the most prevalent RNA modification in eukaryotes. As the critical N6-methyladenosine (m6A) methyltransferase, the roles of methyltransferase like 3 (METTL3) in colorectal cancer (CRC) are controversial. Here, we confirmed that METTL3, a critical m6A methyltransferase, could facilitate CRC progression in vitro and in vivo. Further, we found METTL3 promoted CRC cell proliferation by methylating the m6A site in 3′-untranslated region (UTR) of CCNE1 mRNA to stabilize it. Moreover, we found butyrate, a classical intestinal microbial metabolite, could down-regulate the expression of METTL3 and related cyclin E1 to inhibit CRC development. METTL3 promotes CRC proliferation by stabilizing CCNE1 mRNA in an m6A-dependent manner, representing a promising therapeutic strategy for the treatment of CRC. 相似文献
228.
229.
230.
Xu Wang Yujia Chen Wei Liu Tao Liu Di Sun 《Journal of cellular and molecular medicine》2020,24(17):9908-9924
Hsa_circ_0128846 was found to be the most significantly up‐regulated circRNA in our bioinformatics analysis. However, the role of hsa_circ_0128846 in colorectal cancer has not been explored. We thus aim to explore the influence and mechanism of hsa_circ_0128846 in colorectal cancer by sponging its downstream miRNA target miR‐1184. We collected 40 colorectal cancer patients’ tumour tissues to analyse the expression of hsa_circ_0128846, miR‐1184 and AJUBA using qRT‐PCR and Western blot where needed. Then, we constructed stably transfected SW480 and HCT116 cells to study the influence of hsa_circ_0128846, miR‐1184 and AJUBA on colorectal cancer cell phenotypes. To obtain reliable results, a plethora of experiments including RNA immunoprecipitation assay, flow cytometry, EdU incorporation assay, wound healing migration assay, transwell invasion assay and live imaging of nude mice xenograft assay were performed. The binding relationship between hsa_circ_0128846, miR‐1184 and AJUBA mRNA in colorectal cancer was validated by reported gene assay. In colorectal cancer tissues, circ_0128846 and AJUBA were both significantly up‐regulated, while miR‐1184 was significantly down‐regulated compared with healthy tissues. Meanwhile, hsa_circ_0128846 can absorb miR‐1184 to promote the progression of CRC in vivo and SW480 and HCT116 cell phenotypes in vitro. The knockdown of AJUBA, a downstream target of miR‐1184, reversed the effect of miR‐1184 in CRC cells via enhancing the phosphorylation of the Hippo/YAP signalling pathway proteins MST1, LATS1 and YAP. This study revealed that hsa_circ_0128846 contributed to the development of CRC by decreasing the expression of miR‐1184, thereby increasing AJUBA expression and inactivating Hippo/YAP signalling. 相似文献