全文获取类型
收费全文 | 4220篇 |
免费 | 392篇 |
国内免费 | 203篇 |
出版年
2023年 | 31篇 |
2022年 | 71篇 |
2021年 | 128篇 |
2020年 | 109篇 |
2019年 | 123篇 |
2018年 | 174篇 |
2017年 | 121篇 |
2016年 | 176篇 |
2015年 | 273篇 |
2014年 | 313篇 |
2013年 | 292篇 |
2012年 | 424篇 |
2011年 | 340篇 |
2010年 | 246篇 |
2009年 | 208篇 |
2008年 | 251篇 |
2007年 | 232篇 |
2006年 | 229篇 |
2005年 | 192篇 |
2004年 | 169篇 |
2003年 | 155篇 |
2002年 | 120篇 |
2001年 | 64篇 |
2000年 | 47篇 |
1999年 | 51篇 |
1998年 | 21篇 |
1997年 | 24篇 |
1996年 | 20篇 |
1995年 | 19篇 |
1994年 | 17篇 |
1993年 | 10篇 |
1992年 | 15篇 |
1991年 | 15篇 |
1990年 | 14篇 |
1989年 | 10篇 |
1988年 | 12篇 |
1987年 | 9篇 |
1986年 | 10篇 |
1985年 | 12篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1976年 | 5篇 |
1973年 | 4篇 |
1971年 | 5篇 |
1967年 | 2篇 |
1966年 | 3篇 |
排序方式: 共有4815条查询结果,搜索用时 31 毫秒
61.
Hogyoung Kim Zakaria Y Abd Elmageed Jihang Ju Amarjit S Naura Asim B Abdel-Mageed Shibu Varughese Dennis Paul Suresh Alahari Andrew Catling Jong G Kim A Hamid Boulares 《Molecular medicine (Cambridge, Mass.)》2013,19(1):253-262
Although a relationship between PDZK1 expression and estrogen receptor (ER)-α stimulation has been suggested, the nature of such a connection and the function of PDZK1 in breast cancer remain unknown. Human tissue microarrays (cancer tissue: 262 cores; normal tissue: 87 cores) and breast cancer cell lines were used to conduct the study. We show that PDZK1 protein expression is tightly correlated with human breast malignancy, is negatively correlated with age and had no significant correlation with ER-α expression levels. PDZK1 exhibited an exclusive epithelial expression with mostly cytosolic subcellular localization. Additionally, 17β-estradiol induced PDZK1 expression above its basal level more than 24 h after treatment in MCF-7 cells. PDZK1 expression was indirectly regulated by ER-α stimulation, requiring insulinlike growth factor 1 receptor (IGF-1R) expression and function. The molecular link between PDZK1 and IGF-1R was supported by a significant correlation between protein and mRNA levels (r = 0.591, p < 0.001, and r = 0.537, p < 0.001, respectively) of the two factors in two different cohorts of human breast cancer tissues. Interestingly, PDZK1 knockdown in MCF-7 cells blocked ER-dependent growth and reduced c-Myc expression, whereas ectopic expression of PDZK1 enhanced cell proliferation in the presence or absence of 17β-estradiol potentially through an increase in c-Myc expression, suggesting that PDZK1 has oncogenic activity. PDKZ1 also appeared to interact with the Src/ER-α/epidermal growth factor receptor (EGFR) complex, but not with IGF-1R and enhanced EGFR-stimulated MEK/ERK1/2 signaling. Collectively, our results clarify the relationship between ER-α and PDZK1, propose a direct relationship between PDZK1 and IGF-1R, and identify a novel oncogenic activity for PDZK1 in breast cancer. 相似文献
62.
Hyo-Kyoung Won So-Jung Park Dong-Kyu Kim Myeung Ju Shin Nari Kim Song-Hee Lee Young-Chul Kwon Han Kyu Ko Hyeon-Su Ro Hyun-Sook Lee 《Journal of microbiology (Seoul, Korea)》2013,51(1):118-122
A mycovirus was isolated from an edible mushroom, Lentinula edodes, that was suffering from a severe epidemic. Fractionation of the diseased cell extract by isopycnic centrifugation with 50% CsCl revealed that the diseased mushroom was infected by Lentinula edodes spherical virus (LeSV), a new spherical virus with a diameter of 55 nm. The particle of LeSV encapsidated the 12 kb RNA genome by a 120 kDa coat protein. BLAST analysis of the partially sequenced LeSV genome showed 95% sequence identity with a putative RNA-dependent RNA polymerase (RdRp) gene of the mycovirus HKB, which was previously reported as being a double-stranded RNA (dsRNA) element. In contrast to HKB, the RNA genome in LeSV is encapsidated by the 120 kDa coat protein. To confirm that the LeSV coat protein is encoded by the viral genome, the N-terminal amino acid sequence of the coat protein was determined. The resulting N-terminal amino acid sequence, N-SALDVAPVVPELYFXXLEV-C, was found to be located in the middle of the HKB ORF1, suggesting that the LeSV coat protein was indeed encoded by the virus. To detect LeSV in L. edodes, a primer set targeting the RdRp gene was designed based on the partial sequence of the LeSV genome. RT-PCR analysis showed that 56 of the 84 commercially available dikaryotic cultivars carry LeSV. The transmission pattern of the virus was determined by analysing basidiospores from LeSV-infected and LeSV-free fruiting bodies. Nine out of 10 basidiospores from the LeSV-infected cultivars contained the virus while the spores from the LeSV-free parent were free of LeSV, suggesting that vertical transmission is the primary mode of LeSV propagation. 相似文献
63.
64.
Sanhao Ji Yong Ju Hua Fu Yufen Zhao Tommy Johansson Jacek Stawinski 《Nucleosides, nucleotides & nucleic acids》2013,32(7):771-784
2-,3-,4-Pyridylphosphonates and their phosphonothioate congeners were analyzed by electrospray ionization multistage tandem mass spectrometry (ESI-MSn). It was found that the fragmentation pathways of these compounds were not influenced to any detectable extent by the stereochemistry at the phosphorus centers but were sensitive to the position of a nitrogen atom in the pyridine ring of these compounds. Possible mechanisms for fragmentations of the investigated compounds are discussed in detail. 相似文献
65.
66.
The physiological ecology of Prasiola stipitata was examined in situ from two supralittoral sites in the Bay of Fundy (Nova Scotian, Canada) during November 2011, when the population was undergoing major expansion. Photosynthetic parameters (effective quantum yield, ΦPSII, maximum quantum yield, Fv/Fm, and relative electron transport rate, rETR) were evaluated using chlorophyll fluorescence of PSII. A largely shaded and continuously moist population showed no change in ΦPSII from one hour after sunrise to sunset in which natural irradiance varied between 3 and 300 μmol photons m?2 s?1. High irradiance (up to 1800 μmol photons m?2 s?1) had no apparent negative impacts on either quantum yield or rETR, but high desiccation in the field reduced quantum yield to almost zero. When thalli were brought into the laboratory, no change in Fv/Fm was observed up to 60% dehydration; however, there was a steep decline in Fv/Fm between 60% and 85% dehydration. Thalli showed complete recovery of Fv/Fm within one hour of reimmersion in seawater after 2 days of desiccation. After 15 days of desiccation full recovery required 24 h and after 30 days of desiccation thalli showed only partial recovery. These observations confirm the adaptation to photosynthesis in high irradiances and the rapid recovery following extreme desiccation observed in other Prasiola species. 相似文献
67.
A new species, Obolarina persica, is described from Iran. It is widely associated with dying Quercus brantii, on which it produces charcoal-like stromata. The fungus described herein differs from the other described species, Ob. dryophila, primarily in its much larger ascospores. 相似文献
68.
Silkworm hemolymph (SH) was found to exhibit anti-apoptotic activities in mammalian and insect cell systems. An anti-apoptotic mechanism of SH was investigated in a staurosporine-induced HeLa cell using flow cytometry, caspase assay, Immunoblot, and Immunochemistry. The addition of 5% SH to the medium resulted in lower intracellular activities of caspase-3 and caspase-9 after 0.6 μM of staurosporine treatment; however, SH did not directly inhibit the activities of those enzymes. This suggests SH inhibits the event upstream of these caspase activation steps, such as mitochondrial level events. We found from Immunoblot and Immunochemistry that cytochrome c release from the mitochondria was blocked by SH. SH also inhibited Bax translocation to the mitochondria. On the contrary, SH did not block the apoptosis when Bax is not involved in promoting apoptosis. With these results, we propose that SH protects mitochondria from apoptosis signal via blocking Bax translocation, and the subsequent apoptotic events are then inhibited. The inhibition of apoptosis using SH and its components may lead to new approaches for the minimization of cell death during commercial animal cell cultures. 相似文献
69.
Chen Tian Guoguang Zheng Zhipan Cao Qiao Li Zhenyu Ju Jinhong Wang Weiping Yuan Tao Cheng 《Cell cycle (Georgetown, Tex.)》2013,12(2):322-334
Normal hematopoiesis is suppressed during the development of leukemia. In the T-ALL leukemia mouse model described in our recent study (Hu X, et al. Blood 2009), the impacts of leukemic environment on normal hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were distinct, in that normal HSCs were preserved in part because of increased mitotic quiescence of HSCs and resulting exhaustion of HPCs proliferation. Stem cell factor (SCF) secreted by leukemic cells in Nalm6 B-ALL model was previously suggested to force normal HSCs/HPCs out of their bone marrow niches and allow leukemic cells to occupy the niches (Colmone A, et al. Science 2008). Here we found that stem cell factor (SCF) expression in PB and BM of T-ALL model was increased, but SCF mRNA and protein levels in normal hematopoietic cells were higher than those in leukemia cells, which suggested that upregulated SCF was mainly contributed by non-leukemic cells in response to the leukemia development. To further elucidate the molecular mechanisms, microarray analysis was conducted on normal HSCs in this model and verified by real-time RT-PCR. The expression of Hes1 and its downstream target p21 were elevated in normal HSCs, whereas their expression showed no significant alteration in HPCs. Interestingly, although overexpression of Hes1 by retroviral infection inhibited the in vitro colony formation of normal hematopoietic cells, in vivo results demonstrated that normal Lin- cells and HSPCs were better preserved when normal Lin- cells with Hes1 overexpression were co-transplanted with T-ALL leukemia cells. Our results suggested that the differential expression of Hes1 between HSCs and HPCs resulted in the distinct responses of these cells to the leukemic condition, and that overexpression of Hes1 could enhance normal HSPCs in the leukemic environment. 相似文献
70.
Jun Seo Goo Yo Na Kim Kyung Mi Choi In Sik Hwang Ji Eun Kim Young Ju Lee Moon Hwa Kwak Sun Bo Shim Seung Wan Jee Chul Joo Lim Je Kyung Seong Dae Youn Hwang 《Clinical proteomics》2013,10(1):10