全文获取类型
收费全文 | 1783篇 |
免费 | 137篇 |
国内免费 | 105篇 |
出版年
2024年 | 2篇 |
2023年 | 11篇 |
2022年 | 41篇 |
2021年 | 76篇 |
2020年 | 44篇 |
2019年 | 69篇 |
2018年 | 63篇 |
2017年 | 45篇 |
2016年 | 86篇 |
2015年 | 118篇 |
2014年 | 126篇 |
2013年 | 135篇 |
2012年 | 159篇 |
2011年 | 128篇 |
2010年 | 89篇 |
2009年 | 79篇 |
2008年 | 87篇 |
2007年 | 86篇 |
2006年 | 82篇 |
2005年 | 78篇 |
2004年 | 59篇 |
2003年 | 61篇 |
2002年 | 54篇 |
2001年 | 38篇 |
2000年 | 20篇 |
1999年 | 33篇 |
1998年 | 17篇 |
1997年 | 10篇 |
1996年 | 14篇 |
1995年 | 14篇 |
1994年 | 15篇 |
1993年 | 8篇 |
1992年 | 10篇 |
1991年 | 13篇 |
1990年 | 6篇 |
1989年 | 9篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 9篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1980年 | 1篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1970年 | 2篇 |
排序方式: 共有2025条查询结果,搜索用时 31 毫秒
41.
Junping Li Libin Liang Li Jiang Qian Wang Xia Wen Yuhui Zhao Pengfei Cui Yaping Zhang Guangwen Wang Qibing Li Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Yongping Jiang Liling Liu Hualan Chen Chengjun Li 《PLoS pathogens》2021,17(2)
Posttranslational modifications, such as SUMOylation, play specific roles in the life cycle of invading pathogens. However, the effect of SUMOylation on the adaptation, pathogenesis, and transmission of influenza A virus (IAV) remains largely unknown. Here, we found that a conserved lysine residue at position 612 (K612) of the polymerase basic protein 1 (PB1) of IAV is a bona fide SUMOylation site. SUMOylation of PB1 at K612 had no effect on the stability or cellular localization of PB1, but was critical for viral ribonucleoprotein (vRNP) complex activity and virus replication in vitro. When tested in vivo, we found that the virulence of SUMOylation-defective PB1/K612R mutant IAVs was highly attenuated in mice. Moreover, the airborne transmission of a 2009 pandemic H1N1 PB1/K612R mutant virus was impaired in ferrets, resulting in reversion to wild-type PB1 K612. Mechanistically, SUMOylation at K612 was essential for PB1 to act as the enzymatic core of the viral polymerase by preserving its ability to bind viral RNA. Our study reveals an essential role for PB1 K612 SUMOylation in the pathogenesis and transmission of IAVs, which can be targeted for the design of anti-influenza therapies. 相似文献
42.
Mengtian Fan Jinghong Wu Xian Li Yingjiu Jiang Xiaowen Wang Mengjun Bie Yaguang Weng Sicheng Chen Bin Chen Liqin An Menghao Zhang Gaigai Huang Mengying Zhu Qiong Shi 《Journal of cellular and molecular medicine》2021,25(1):132-146
It has been reported that chemokine CX3CL1 can regulate various tumours by binding to its unique receptor CX3CR1. However, the effect of CX3CL1-CX3CR1 on the lung adenocarcinoma and lung squamous cell carcinoma is still unclear. Here, we showed that CX3CL1 can further invasion and migration of lung adenocarcinoma A549 and lung squamous cell carcinoma H520. In addition, Western blot and immunofluorescence test indicated CX3CL1 up-regulated the phosphorylation level of cortactin, which is a marker of cell pseudopodium. Meanwhile, the phosphorylation levels of c-Src and c-Abl, which are closely related to the regulation of cortactin phosphorylation, are elevated. Nevertheless, the src/abl inhibitor bosutinib and mutations of cortactin phosphorylation site could inhibit the promotion effect of CX3CL1 on invasion and migration of A549 and H520. Moreover, these results of MTT, Hoechst staining and Western blot suggested that CX3CL1 had no effect on the proliferation and apoptosis of A549 and H520 in vitro. The effects of CX3CL1 were also verified by the subcutaneous tumour formation in nude mice, which showed that it could promote proliferation and invasion of A549 in vivo. In summary, our results indicated that CX3CL1 furthered invasion and migration in lung cancer cells partly via activating cortactin, and CX3CL1 may be a potential molecule in regulating the migration and invasion of lung cancer. 相似文献
43.
Zilan Lv Dandan Yang Jie Li Min Hu Min Luo Xiaoqin Zhan Peipei Song Chen Liu Huili Bai Baolin Li Yang Yang Yingying Chen Qiong Shi Yaguang Weng 《Molecules and cells》2013,36(2):119-126
Transforming growth factor-β (TGF-β) is known to promote tumor migration and invasion. Bone morphogenetic proteins (BMPs) are members of the TGF-β family expressed in a variety of human carcinoma cell lines. The role of bone morphogenetic protein 9 (BMP9), the most powerful osteogenic factor, in osteosarcoma (OS) progression has not been fully clarified. The expression of BMP9 and its receptors in OS cell lines was analyzed by RT-PCR. We found that BMP9 and its receptors were expressed in OS cell lines. We further investigated the influence of BMP9 on the biological behaviors of OS cells. BMP9 overexpression in the OS cell lines 143B and MG63 inhibited in vitro cell migration and invasion. We further investigated the expression of a panel of cancer-related genes and found that BMP9 overexpression increased the phosphorylation of Smad1/5/8 proteins, increased the expression of ID1, and reduced the expression and activity of matrix metalloproteinase 9 (MMP9) in OS cells. BMP9 silencing induced the opposite effects. We also found that BMP9 may not affect the chemokine (C-X-C motif) ligand 12 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis to regulate the invasiveness and metastatic capacity of OS cells. Interestingly, CXCR4 was expressed in both 143B and MG63 cells, while CXCL12 was only detected in MG63 cells. Taken together, we hypothesize that BMP9 inhibits the migration and invasiveness of OS cells through a Smad-dependent pathway by downregulating the expression and activity of MMP9. 相似文献
44.
This study investigated how the current economic recession (since December 2007) has affected dog and cat relinquishment, adoption, and euthanasia at the Anti-Cruelty Society animal shelter in Chicago, Illinois. The study compared temporal patterns of the investigated statistics before (2000–2007) the start of the current recession with the patterns after the start of the recession (2008–2010). The results showed that once the guardianship (ownership) of a nonhuman animal had been established, the recession did not greatly affect the owner's decision on relinquishment—except for the relinquishment of senior dogs, which may be associated with increased costs of care. However, an unfavorable economic environment may have reduced adoption of animals. The consequences of a decline in adoptions might be reflected in an increase in the proportion or number of sheltered animals euthanized. This study demonstrated how monitoring changes in temporal patterns in these shelter statistics can help guide animal shelters to better prepare for the current recession. 相似文献
45.
Ji-Hong Hu Jing-Jing Nie Zhen-Xiang Gao Qing-Hua Weng Zhen-He Wang Chuan-Bao Li 《Free radical research》2013,47(9):961-969
AbstractEmerging evidence suggests that microbial pathogens may induce oxidative stress in infected hosts. The aim of the present study was to investigate the relationship between changes in oxidative stress and intestinal infection with and without antibiotic treatment in animal models. Sprague-Dawley (SD) rats were divided into three groups: rats infected with Salmonella enterica serovar Enteritidis (S. enteritidis), rats infected with S. enteritidis followed by norfloxacin treatment, and the control group. To evaluate oxidative stress changes, levels of 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) and 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dGsn), which represented oxidative damage to RNA and DNA, respectively, were analysed in urine and tissue samples. In urine, the level of 8-oxo-Gsn increased significantly after oral exposure to S. enteritidis (p?≤?0.001) and returned to baseline after recovery. Notably, norfloxacin treatment decreased the level of 8-oxo-Gsn in urine significantly (p?=?0.001). Changes of 8-oxo-Gsn measured in tissues from the small intestine, colon, liver and spleen were consistent with 8-oxo-Gsn measured in urine. Our study suggested that 8-oxo-Gsn in urine may serve as a highly sensitive biomarker for evaluating the severity of S. enteritidis infection and the effectiveness of antibiotic treatment against infection. 相似文献
46.
Marcel Brokbartold Erwin J. M. Temminghoff Liping Weng Bernd Marschner 《Soil & Sediment Contamination》2013,22(8):839-855
Red lead (Pb3O4) has been extensively used in the past in anti-corrosion paints for the protection of steel constructions such as electricity pylons or bridges. Until recently, little has been known about the behavior of these Pb compounds in soils. Therefore, three pylon soils and six red lead anti-corrosion paints were characterized in terms of solubility, Pb mineral composition, extractability, sorption and desorption, and the chemical speciation of Pb in soil extracts. The pylon soils were characterized by moderate total Pb concentrations (≈700 mg kg?1), while NH4NO3 extractable Pb was exceptionally high (up to 15% of total Pb). In soil extracts, the free Pb2+ fraction ranged from 33 to 81% of total soluble Pb. The equilibrium concentration of Pb derived from Pb3O4 in ultra-pure water reached 68.5 mg L?1. This high solubility explains the observed high extractability in soils and contradicts earlier reports of much lower water solubilities of the compound. 相似文献
47.
Susan Walker Mark Danton Edward Weng Koon Peng Fiona Lyall 《Cell stress & chaperones》2013,18(3):269-277
Tetralogy of Fallot (TOF) is a congenital heart condition in which the right ventricle is exposed to cyanosis and pressure overload. Patients have an increased risk of right ventricle dysfunction following corrective surgery. Whether the cyanotic myocardium is less tolerant of injury compared to non-cyanotic is unclear. Heat shock proteins (HSPs) protect against cellular stresses. The aim of this study was to examine HSP 27 expression in the right ventricle resected from TOF patients and determine its relationship with right ventricle function and clinical outcome. Ten cyanotic and ten non-cyanotic patients were studied. Western blotting was used to quantify HSP 27 in resected myocardium at (1) baseline (first 15 min of aortic cross clamp and closest representation of pre-operative status) and (2) after 15 min during ischemia until surgery was complete. The cyanotic group had significantly increased haematocrit, lower O2 saturation, thicker interventricular septal wall thickness and released more troponin-I on post-operative day 1 (p?<?0.05). HSP 27 expression was significantly increased in the <15 min cyanotic compared to the <15 min non-cyanotic group (p?=?0.03). In the cyanotic group, baseline HSP 27 expression also significantly correlated with oxygen extraction ratio (p?=?0.028), post-operative basal septal velocity (p?=?0.036) and mixed venous oxygen saturation (p?=?0.02), markers of improved cardiac output/contraction. Increased HSP 27 expression and associated improved right ventricle function and systemic perfusion supports a cardio-protective effect of HSP 27 in cyanotic TOF. 相似文献
48.
Fagen Li Fan Yang Qijie Weng Guangtian Yin Mei Li Siming Gan 《Molecular breeding : new strategies in plant improvement》2013,31(4):867-877
Rattans serve as an important source of raw non-wood materials for furniture and handicraft industries worldwide. However, their genomic sequence information in public databases is very limited. In this study, a set of 2,528 good-quality expressed sequence tags (ESTs) were generated from a full-length cDNA library constructed previously with root, stem and male inflorescence tissues of Calamus simplicifolius C. F. Wei, a rattan species native to Hainan Island, China. The ESTs were assembled into 1,588 unigenes, including 1,221 singletons and 367 contigs. BlastX searches against the GenBank non-redundant protein database revealed that 1,248 (78.6 %) unigenes had at least one significant match (E ≤ 10?5). The gene ontology functional classification assigned 991, 669 and 977 of the unigenes to the cellular component, molecular function and biological process categories, respectively. A total of 71 simple sequence repeat (SSR) loci were developed among these ESTs, including 65 polymorphic across 19 rattan species representing three genera. High levels of cross-species/genus transferability were observed for the EST-SSRs. For the polymorphic EST-SSR markers, the number of alleles per locus and polymorphic information content ranged from 2 to 25 (mean 11.1) and from 0.135 to 0.949 (mean 0.695), respectively. The EST sequences and the EST-SSR primers have been deposited in GenBank databases of EST (IDs JK838364–40891) and Probe (IDs Pr16718978–9048, to be assigned). 相似文献
49.
Chih-Shin Lin Charlene Lin Shih-Feng Weng Shih-Wei Lin Yung-Song Lin 《Cancer epidemiology》2013,37(5):719-724
Objectives: HIV-related immunosuppression has been associated with the development of AIDS-defining malignancies. We examined the overall survival of HIV-infected patients who developed cancer. Design: A retrospective cohort study. Methods: Using the Taiwan Longitudinal Health Insurance Database, we compared patients diagnosed with HIV (n = 9918) between January 1, 2002, and December 31, 2007 with age-matched controls (n = 99,180). Each patient was followed until the end of 2009 (least 2 years after the initial HIV diagnosis) to evaluate the incidence of malignancies. Results: The risk of overall malignancies in the HIV-infected cohort was 1.88 times higher than the risk of a first malignancy in the age-matched non-HIV infected cohort (incidence rate ratio [IRR]) = 2.05, p < 0.0001). The diagnosis of a malignancy was negatively correlated with survival in the HIV-infected cohort (p < 0.0011), and HIV infection had a synergistic effect on the survival of patients with malignancies compared with the non-HIV infected cohort, all of who had been newly diagnosed with cancer (p < 0.0001). However, the difference in the risk of developing nasopharyngeal carcinoma (NPC), a highly prevalent malignancy in Taiwan, between the two cohorts was not significant (IRR = 0.22, 95% CI = 0.03–1.65). Conclusions: The risk of cancer in HIV-infected patients in Taiwan has increased significantly in the era of highly active antiretroviral therapy. A history of HIV significantly affected the survival of the patients in our study cohort after they developed cancer.Evidence level: 2B. 相似文献
50.
Yen-Chu Huang Ho-Ling Liu Jiann-Der Lee Jen-Tsung Yang Hsu-Huei Weng Meng Lee Mei-Yu Yeh Yuan-Hsiung Tsai 《PloS one》2013,8(7)