全文获取类型
收费全文 | 7634篇 |
免费 | 671篇 |
国内免费 | 879篇 |
出版年
2024年 | 31篇 |
2023年 | 148篇 |
2022年 | 321篇 |
2021年 | 544篇 |
2020年 | 393篇 |
2019年 | 460篇 |
2018年 | 407篇 |
2017年 | 327篇 |
2016年 | 381篇 |
2015年 | 554篇 |
2014年 | 653篇 |
2013年 | 618篇 |
2012年 | 779篇 |
2011年 | 633篇 |
2010年 | 419篇 |
2009年 | 331篇 |
2008年 | 327篇 |
2007年 | 300篇 |
2006年 | 233篇 |
2005年 | 209篇 |
2004年 | 145篇 |
2003年 | 112篇 |
2002年 | 134篇 |
2001年 | 104篇 |
2000年 | 72篇 |
1999年 | 78篇 |
1998年 | 68篇 |
1997年 | 48篇 |
1996年 | 43篇 |
1995年 | 36篇 |
1994年 | 47篇 |
1993年 | 25篇 |
1992年 | 22篇 |
1991年 | 24篇 |
1990年 | 25篇 |
1989年 | 26篇 |
1988年 | 17篇 |
1987年 | 20篇 |
1986年 | 17篇 |
1985年 | 10篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1982年 | 3篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1973年 | 2篇 |
1970年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有9184条查询结果,搜索用时 15 毫秒
771.
Meng Zhang Shulian Xie Xiaojing Han Yuyuan He Jia Feng Ying Shi 《Journal of phycology》2010,46(2):390-395
Four populations of charophytes (including three species), Chara inconnexa T. F. Allen (populations 1 and 2), C. vulgaris L., and Nitellopsis obtusa (Desv.) J. Groves, were studied for effective chemicals as oviposition deterrents of Culex pipiens pallens. The charophyte volatile organic compounds (VOCs) were retained in Tenax GR, subsequently desorbed using a thermal desorption cold trap injector (TCT), and analyzed by gas chromatography/mass spectrometry (GC/MS) to elucidate that charophytes have repellent properties. C. inconnexa (1) and C. inconnexa (2) exhibited strong repellent activities, and C. vulgaris showed some repellent activity against C. pipiens pallens with terpenes and benzothiazole playing major roles, while N. obtusa lacked those compounds and did not have an effect. These results suggest that charophytes have potential application as pesticides, but there are interspecific differences. In addition, benzene hydrocarbons were among the volatiles in Chara but not in N. obtusa, implying that some charophytes could be used to absorb these compounds. 相似文献
772.
773.
γ-Protocadherins (PCDH-γ) regulate neuronal survival in the vertebrate central nervous system. The molecular mechanisms of how PCDH-γ mediates this function are still not understood. In this study, we show that through their common cytoplasmic domain, different PCDH-γ isoforms interact with an intracellular adaptor protein named PDCD10 (programmed cell death 10). PDCD10 is also known as CCM3, a causative genetic defect for cerebral cavernous malformations in humans. Using RNAi-mediated knockdown, we demonstrate that PDCD10 is required for the occurrence of apoptosis upon PCDH-γ depletion in developing chicken spinal neurons. Moreover, overexpression of PDCD10 is sufficient to induce neuronal apoptosis. Taken together, our data reveal a novel function for PDCD10/CCM3, acting as a critical regulator of neuronal survival during development. 相似文献
774.
Sha Meng Min Luo He Sun Xin Yu Meili Shen Quancang Zhang Rudan Zhou Xiaofang Ju Wei Tao Di Liu Hongkui Deng Zhigang Lu 《The Journal of biological chemistry》2010,285(43):33219-33229
Bmi-1, the first functionally identified polycomb gene family member, plays critical roles in cell cycle regulation, cell immortalization, and cell senescence. Bmi-1 is involved in the development and progression of carcinomas and is a potent target for cancer therapy. One important pathway regulated by Bmi-1 is that involving two cyclin-dependent kinase inhibitors, p16Ink4a and p19Arf, as Bmi-1 represses the INK4a locus on which they are encoded. A close correlation between the up-regulation of Bmi-1 and down-regulation of p16 has been demonstrated in various tumors; however, how Bmi-1 regulates p16 expression is not clear. In this study, we revealed that Bmi-1 regulates the expression of p16 by binding directly to the Bmi-1-responding element (BRE) within the p16 promoter. The BRE resided at bp −821 to −732 upstream of the p16 ATG codon. BRE alone was sufficient to allow Bmi-1-mediated regulation of the CMV promoter. Bmi-1 typically functions by forming a complex with Ring2; however, regulation of p16 was independent of Ring2. Chromatin immunoprecipitation sequencing of Bmi-1-precipitated chromatin DNA revealed that 1536 genes were targeted by Bmi-1, including genes involved in tissue-specific differentiation, cell cycle, and apoptosis. By analyzing the binding sequences of these genes, we found two highly conserved Bmi-1-binding motifs, which were required for Bmi-1-mediated p16 promoter regulation. Taken together, our results revealed the molecular mechanism of Bmi-1-mediated regulation of the p16 gene, thus providing further insights into the functions of Bmi-1 as well as a sensitive high-throughput platform with which to screen Bmi-1-targeted small molecules for cancer therapy. 相似文献
775.
Novel Function and Intracellular Localization of Methionine Adenosyltransferase 2β Splicing Variants
Meng Xia Yongheng Chen Ling-Chi Wang Ebrahim Zandi Heping Yang Sean Bemanian M. Luz Martínez-Chantar José M. Mato Shelly C. Lu 《The Journal of biological chemistry》2010,285(26):20015-20021
Human methionine adenosyltransferase 2β (MAT2β) encodes for two major splicing variants, V1 and V2, which are differentially expressed in normal tissues. Both variants are induced in human liver cancer and positively regulate growth. The aim of this work was to identify interacting proteins of V1 and V2. His-tagged V1 and V2 were overexpressed in Rosetta pLysS cells, purified, and used in a pulldown assay to identify interacting proteins from human colon cancer cell line RKO cell lysates. The eluted lysates were subjected to Western blot and in solution proteomic analyses. HuR, an mRNA-binding protein known to stabilize the mRNA of several cyclins, was identified to interact with V1 and V2. Immunoprecipitation and Western blotting confirmed their interaction in both liver and colon cancer cells. These variant proteins are located in both nucleus and cytoplasm in liver and colon cancer cells and, when overexpressed, increased the cytoplasmic HuR content. This led to increased expression of cyclin D1 and cyclin A, known targets of HuR. When endogenous expression of V1 or V2 is reduced by small interference RNA, cytoplasmic HuR content fell and the expression of these HuR target genes also decreased. Knockdown of cyclin D1 or cyclin A blunted, whereas knockdown of HuR largely prevented, the ability of V1 or V2 overexpression to induce growth. In conclusion, MAT2β variants reside mostly in the nucleus and regulate HuR subcellular content to affect cell proliferation. 相似文献
776.
Zhaobing Gao Tangzhi Zhang Meng Wu Qiaojie Xiong Haiyan Sun Yinan Zhang Liansuo Zu Wei Wang Min Li 《The Journal of biological chemistry》2010,285(36):28322-28332
Kv7 channels, especially Kv7.2 (KCNQ2) and Kv7.3 (KCNQ3), are key determinants for membrane excitability in the brain. Some chemical modulators of KCNQ channels are in development for use as anti-epileptic drugs, such as retigabine (D-23129, N-(2-amino-4-(4-fluorobenzylamino)-phenyl)), which was recently approved for clinical use. In addition, several other compounds were also reported to potentiate activity of the Kv7 channels. It is therefore of interest to investigate compound-channel interactions, so that more insights may be gained to aid future development of therapeutics. We have conducted a screen of 20,000 compounds for KCNQ2 potentiators using rubidium flux combined with atomic absorption spectrometry. Here, we report the characterization of a series of new structures that display isoform specificity and induce a marked reduction of deactivation distinct from that of retigabine. Furthermore, KCNQ2(W236L), a previously reported mutation that abolishes sensitivity to retigabine, remains fully sensitive to these compounds. This result, together with mutagenesis and other studies, suggests that the reported compounds confer a unique mode of action and involve new molecular determinants on the channel protein, consistent with the idea of recognizing a new site on channel protein. 相似文献
777.
778.
There is still a considerable lack of quantitative information concerning the effects of stent structures on blood flow in an aneurismal cavity. In this paper, five virtual stents with different structures and wire cross-sections were designed for incorporation into the same patient-specific aneurysm model. Computational fluid dynamics simulations were performed so as to study how these five types of stents modified hemodynamic parameters. Numerical results demonstrated that the mean flow rate in the aneurismal cavity decreased the most in the model that used a stent with a rectangular wire cross-section, and that the wall shear stresses at the dome and neck of the aneurysm decreased more in models that used a stent with a circular wire cross-section or a spiral stent with a rectangular wire cross-section compared to other models. In addition, the wall pressure on the aneurysm increased slightly after implantation of the stent in all five models. This result differs from that previously published, and may help guide the design and assist clinicians in selecting an appropriate stent for treating cerebral aneurysms. 相似文献
779.
Yan Zhou Peng Pan Lu Yao Meng Su Ping He Na Niu Michael A. McNutt Jiang Gu 《The journal of histochemistry and cytochemistry》2010,58(4):309-316
Human cardiac stem/progenitor cells and their potential for repair of heart injury are a current hot topic of research. CD117 has been used frequently as a marker for identification of stem/progenitor cells in the heart. However, cardiac mast cells, which are also CD117+, have not been excluded by credible means when selecting putative cardiac progenitors by using CD117 as a marker. We evaluated the relationship between CD117+ cells and mast cells in the left ventricle of human hearts (n=5 patients, ages 1 week–75 years) with the well-established mast cell markers tryptase, toluidine blue, and thionine. A large number (85–100%) of CD117+ cells in the human heart were specifically identified as mast cells. In addition, mast cells showed weak or moderate CD45 immunostaining signals. These results indicate that the majority of CD117+ cells in the heart are mast cells and that these cells are distinctly positive for CD45, although staining was weak or moderate. These results strongly suggest that the newly reported CD117+/CD45dim/moderate putative cardiac progenitor cells are mast cells. The significance of this observation in stem cell research of the heart is discussed. (J Histochem Cytochem 58:309–316, 2010) 相似文献
780.
Meng Luo Xia Liu Yuangang Zu Yujie Fu Su Zhang Liping Yao Thomas Efferth 《Chemico-biological interactions》2010,188(1):151-160
Cajanol (5-hydroxy-3-(4-hydroxy-2-methoxyphenyl)-7-methoxychroman-4-one) is an isoflavanone from Pigeonpea [Cajanus cajan (L.) Millsp.] roots. As the most effective phytoalexin in pigeonpea, the cytotoxic activity of cajanol towards cancer cells has not been report as yet. In the present study, the anticancer activity of cajanol towards MCF-7 human breast cancer cells was investigated. In order to explore the underlying mechanism of cell growth inhibition of cajanol, cell cycle distribution, DNA fragmentation assay and morphological assessment of nuclear change, ROS generation, mitochondrial membrane potential (ΔΨm) disruption, and expression of caspase-3 and caspase-9, Bax, Bcl-2, PARP and cytochrome c were measured in MCF-7 cells. Cajanol inhibited the growth of MCF-7 cells in a time and dose-dependent manner. The IC50 value was 54.05 μM after 72 h treatment, 58.32 μM after 48 h; and 83.42 μM after 24 h. Cajanol arrested the cell cycle in the G2/M phase and induced apoptosis via a ROS-mediated mitochondria-dependent pathway. Western blot analysis showed that cajanol inhibited Bcl-2 expression and induced Bax expression to desintegrate the outer mitochondrial membrane and causing cytochrome c release. Mitochondrial cytochrome c release was associated with the activation of caspase-9 and caspase-3 cascade, and active-caspase-3 was involved in PARP cleavage. All of these signal transduction pathways are involved in initiating apoptosis. To the best of our knowledge, this is the first report demonstrating the cytotoxic activity of cajanol towards cancer cells in vitro. 相似文献