全文获取类型
收费全文 | 1504篇 |
免费 | 93篇 |
国内免费 | 2篇 |
出版年
2023年 | 15篇 |
2022年 | 36篇 |
2021年 | 62篇 |
2020年 | 65篇 |
2019年 | 117篇 |
2018年 | 117篇 |
2017年 | 58篇 |
2016年 | 69篇 |
2015年 | 71篇 |
2014年 | 106篇 |
2013年 | 141篇 |
2012年 | 128篇 |
2011年 | 125篇 |
2010年 | 74篇 |
2009年 | 64篇 |
2008年 | 56篇 |
2007年 | 61篇 |
2006年 | 38篇 |
2005年 | 25篇 |
2004年 | 34篇 |
2003年 | 23篇 |
2002年 | 19篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 8篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 6篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1972年 | 2篇 |
1968年 | 3篇 |
1945年 | 1篇 |
排序方式: 共有1599条查询结果,搜索用时 46 毫秒
71.
Transactivation of epidermal growth factor receptor (EGFR) is a well-documented mechanism by which vasoactive peptides and H2O2 elicit their cellular responses. However, a role for the insulin-like growth factor type-1 receptor (IGF-1R) transactivation in mediating the effects of angiotensin II (Ang II) and H2O2 in vascular smooth muscle cells from different artery types have also been recently recognized. By using a series of pharmacological inhibitors of various growth factor receptor tyrosine kinases and a direct analysis of the phosphorylation status of the beta-subunit of IGF-1R, a requirement of this growth factor receptor in Ang II and H2O2 response has been demonstrated. This review discusses some of the studies that highlight the importance of IGF-1R transactivation in mediating Ang II- and H2O2-induced mitogen-activated protein kinase and protein kinase B signaling pathways. 相似文献
72.
Yousefi R Imani M Ardestani SK Saboury AA Gheibi N Ranjbar B 《Acta biochimica et biophysica Sinica》2007,39(10):795-802
Calprotectin, a heterodimeric complex belonging to the S 100 protein family, has been found predominantly in the cytosolic fraction of neutrophils. In the present study, human calprotectin was purified from neutrophils using two-step ion exchange chromatography. The purified protein was used for circular dichroism study and fluorescence analysis in the presence of calcium and zinc at physiological concentrations, as well as for assessment of its inhibitory activity on the K562 leukemia cell line. The thermal stability of the protein at pH 7.0 (physiological pH) and 8.0 (similar to intestinal pH) was also compared. The results of cell proliferation analysis revealed that human calprotectin initiated growth inhibition of the tumor cells in a dose- dependent manner. The intrinsic fluorescence emission spectra of human calprotectin (50 ktg/ml) in the presence of calcium and zinc ions show a reduction in fluorescence intensity, reflecting a conformational change within the protein with exposure of aromatic residues to the protein surface that is important for the biological function of calprotectin. The far ultraviolet-circular dichroism spectra of human calprotectin in the presence of calcium and zinc ions at physiological concentrations show a decrease in the m-helical content of the protein and an increase in [3- and other structures. Our results also show that increasing the pH level from 7.0 to 8.0 leads to a marked elevation in the thermal stability of human calprotectin, indicating a significant role for pH in the stability of calprotectin in the gut. 相似文献
73.
Lanquar V Kuhn L Lelièvre F Khafif M Espagne C Bruley C Barbier-Brygoo H Garin J Thomine S 《Proteomics》2007,7(5):750-754
An important goal for proteomic studies is the global comparison of proteomes from different genotypes, tissues, or physiological conditions. This has so far been mostly achieved by densitometric comparison of spot intensities after protein separation by 2-DE. However, the physicochemical properties of membrane proteins preclude the use of 2-DE. Here, we describe the use of in vivo labeling by the stable isotope 15N as an alternative approach for comparative membrane proteomic studies in plant cells. We confirm that 15N-metabolic labeling of proteins is possible and efficient in Arabidopsis suspension cells. Quantification of 14N versus 15N MS signals reflects the relative abundance of 14N and 15N proteins in the sample analyzed. We describe the use of 15N-metabolic labeling to perform a partial comparative analysis of Arabidopsis cells following cadmium exposure. By focusing our attention on plasma membrane proteins, we were able to confidently identify proteins showing up to 5-fold regulation compared to unexposed cells. This study provides a proof of principle that 15N-metabolic labeling is a useful technique for comparative membrane proteome studies. 相似文献
74.
75.
International Microbiology - Acanthamoeba spp. and Salmonella share common habitats, and their interaction may influence the biofilm-forming ability of Salmonella. In this study, biofilm formation... 相似文献
76.
Elham Safarzadeh Shahryar Hashemzadeh Pascal H.G. Duijf Behzad Mansoori Vahid Khaze Ali Mohammadi Tohid Kazemi Mehdi Yousefi Milad Asadi Hamed Mohammadi Farhad Babaie Behzad Baradaran 《Journal of cellular physiology》2019,234(4):3515-3525
Evading immune destruction is a hallmark of cancer. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid immune cells, are thought to foster the establishment of an immunosuppressive tumor microenvironment, but it remains unclear how. This study aims to determine the levels of circulating MDSCs and their subpopulations and test their immunosuppressive functions in patients with breast cancer (BC). We analyzed the fractions of MDSCs in freshly isolated peripheral blood mononuclear cells of patients with BC and healthy donors using flow cytometry. Circulating MDSCs were further phenotyped using fluorescently labeled antihuman monoclonal antibodies. Coculture experiments revealed the effects of MDSCs on CD3+ T cell response. Moreover, we correlated circulating MDSC levels with clinicopathological features of patients with BC. We show that the fraction of HLA-DR – CD33 + MDSCs in peripheral blood is about 10-fold higher in patients with BC than in healthy control individuals. The levels of all MDSC subpopulations, including monocytic and granulocytic MDSCs, are significantly elevated. Coculture experiments of purified HLA-DR – CD33 + MDSCs and CD3 + T cells demonstrate that T cell proliferation is more effectively inhibited by BC patient-derived MDSCs than by healthy control MDSCs. Moreover, increased circulating MDSC levels robustly associate with advanced BC stage and positive lymph node status. By being more abundant and more effective T cell suppressors, BC patient-derived circulating MDSCs exert a dual immunosuppressive effect. Our findings pave the way to develop novel diagnostic and immunotherapeutic strategies, aimed at detecting and inhibiting MDSCs in patients with BC. 相似文献
77.
Aynaz Mihanfar Javad Aghazadeh Attari Iraj Mohebbi Maryam Majidinia Mojtaba Kaviani Mehdi Yousefi Bahman Yousefi 《Journal of cellular physiology》2019,234(4):3238-3253
The cancer stem cell (CSC) model encompasses an advantageous paradigm that in recent decades provides a better elucidation for many important biological aspects of cancer initiation, progression, metastasis, and, more important, development of multidrug resistance (MDR). Such several other hematological malignancies and solid tumors and the identification and isolation of ovarian cancer stem cells (OV-CSCs) show that ovarian cancer also follows this hierarchical model. Gaining a better insight into CSC-mediated resistance holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients in the future. Therefore, in this review, we will discuss some important mechanisms by which CSCs can escape chemotherapy, and then review the recent and growing body of evidence that supports the contribution of CSCs to MDR in ovarian cancer. 相似文献
78.
79.
80.
Mehri Abedi Reza Ahangari Cohan Fereidoun Mahboudi Mohammad Ali Faramarzi Ramin Fazel Narges Damavandi Mehdi Shafiee Ardestani Fatemeh Davami 《Journal of cellular physiology》2019,234(10):18206-18213
Antibody-drug conjugates are now of considerable interest and are recommended for the treatment of cancers. Linkers are having a crucial role in potency and efficacy of these drugs. Herein, for the first time, we have used a water-soluble poly-ethylene glycol based linker (succinimidyl-[(N-maleimido propionamido)-diethyleneglycol] [SM(PEG)2]) for lysine amide coupling of DM1 drug to trastuzumab considering evaluation of the effect of using a hydrophilic linker on physicochemical and biological properties of the resulting conjugate in comparison to the conjugate containing succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) linker, which has a relative hydrophobic nature. The physicochemical properties of synthesized conjugates were investigated in terms of drug to antibody ratio, size variants and free drug quantities. In vitro biological activity of trastuzumab-DM1 conjugates was assessed on breast cancer cell lines expressing different levels of HER2 using binding affinity, antiproliferative, apoptosis, and antibody-dependent cell-mediated cytotoxicity (ADCC) assays. Synthesized conjugate containing hydrophilic linker, showed higher drug to antibody ratio, no aggregated form and higher cellular toxicity in comparison to SMCC bearing conjugate. Binding affinity and ADCC potential of conjugates was not affected upon the usage of hydrophilic linker. In conclusion, application of SM(PEG)2 for coupling of DM1 to trastuzumab enhance desirable characteristics of the resulting conjugate. 相似文献