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851.
Zhong-Wei Liu Xiao-Lin Niu Kun-Lun Chen Yu-Jie Xing Xuan Wang Chuan Qiu Deng-Feng Gao 《Biological trace element research》2013,153(1-3):220-228
The possible mechanism of adriamycin (ADR) and/or selenium (Se) deficiency-induced cardiac dysfunction, and cardioprotective effects of Se against ADR-induced cardiac toxicity were investigated in this study. Cardiac function was evaluated by plasma brain natriuretic peptide level and echocardiographic and hemodynamic parameters. Cardiac glutathione peroxidase (GPx) activity was assessed spectrophotometrically. Expression of ATP-sensitive potassium channels (KATP) subunits—SUR2A and Kir6.2—were examined by real-time PCR and Western blotting. The results showed that cardiac function and cardiac GPx activity decreased remarkably after administration of ADR or Se deficiency; more dramatic impairment of cardiac function and cardiac GPx activity were observed after co-administration of ADR and Se deficiency. Mechanically, it is novel for us to find down-regulation of KATP subunits gene expression in cardiac tissue after administration of ADR or Se deficiency, and more significant inhibition of cardiac KATP gene expression was identified after co-administration of ADR and Se deficiency. Furthermore, cardiac toxicity of ADR was found alleviated by Se supplementation, accompanied by restoring of cardiac GPx activity and cardiac KATP gene expression. These results indicate that decreased expression of cardiac KATP is involved in adriamycin and/or Se deficiency-induced cardiac dysfunction; Se deficiency exacerbates adriamycin-induced cardiac dysfunction by future inhibition of KATP expression; Se supplementation seems to protect against adriamycin-induced cardiac dysfunction via restoring KATP expression, showing potential clinical application in cancer chemotherapy. 相似文献
852.
Q. Li X. Z. Li T. Wang L. W. Zhou H. Q. Feng L. Gao J. R. Pei C. Lin C. X. Jiang 《Biological trace element research》2013,151(1):14-17
The aim of the present study was to explore the role of selenoprotein P (SePP) in the etiology of the endemic sudden cardiac death in Yunnan, China. The levels of SePP of 124 subjects and glutathione peroxidase (GPx) of 119 subjects were measured. The subjects were from the old and new endemic areas and non-endemic areas. The levels of SePP and GPx of the subjects of the old endemic area were significantly higher than those of the subjects of the new endemic area and the non-endemic areas, respectively. The Pearson’s correlation among SePP, GPx, and the number of the incident cases of the disease were statistically significant. These correlations show that there is an inverse relationship among the number of patients and the levels of SePP (r? = ?? 0.9800, P ?= ?0.0200) and GPx (r? = ?? 0.961, P ?= ?0.009). The results show that selenium deficiency might play an important role in the incidence of the disease. 相似文献
853.
Wei Zhang Hongqi Feng Yanhui Gao Liyan Sun Jing Wang Yuanyuan Li Cheng Wang Lijun Zhao Xinxin Hu Huixin Sun Yudan Wei Dianjun Sun 《Biological trace element research》2013,151(2):269-276
Although studies have shown that arsenic exposure can induce apoptosis in a variety of cells, the exact molecular mechanism of chronic arsenicosis remains unclear. Based on our previous study on human serum, the present study was to determine whether pigment epithelium-derived factor (PEDF) plays a role in the damage induced by chronic arsenic exposure in a rat model and to explore the possible signaling pathway involved. Thirty male Wistar rats were randomly divided into three groups and the arsenite doses administered were 0, 10, and 50 mg/L, respectively. The experiment lasted for 6 months. Our results showed that level of arsenic increased significantly in serum, liver, brain, and kidney in arsenic-exposed groups. It was indicated that PEDF protein was widely distributed in the cytoplasm of various types of cells in liver, brain, and kidney. PEDF protein level was only changed when the arsenite dose reached 50 mg/L in liver and brain, whereas it was not changed in the kidney. In order to investigate the possible mechanism of PEDF-exerted damages upon arsenite exposure, apoptosis in liver and brain was assessed. The proportion of apoptotic cells gradually increased with increasing arsenic administration. The ratio of Bax/Bcl-2 in the high arsenic group (50 mg/L) was significantly higher than that in the control group. Therefore, we thought PEDF played a role in cell apoptosis of liver and brain which induced by sodium arsenite exposure, and the results also demonstrated that Bax and Bcl-2 might be two key targets in the action of PEDF. 相似文献
854.
Jing Zhang Yang Zhou Lin Ma Shunquan Huang Ruijin Wang Rongrong Gao Youjun Wu Hongjun Shi Jun Zhang 《Biological trace element research》2013,152(2):267-274
Nickel is an important kind of metal and a necessary trace element in people’s production and livelihood; it is also a well-confirmed human carcinogen. In the past few years, researchers did a large number of studies about the molecular mechanisms of nickel carcinogenesis, and they focused on activation of proto-oncogenes and inactivation of anti-oncogenes caused by gene point mutation, gene deletion, gene amplification, DNA methylation, chromosome condensation, and so on that were induced by nickel. However, the researches on tumorigenic molecular mechanisms regulated by microRNAs (miRNAs) are rare. In this study, we established nickel-induced tumor by injecting Ni3S2 compounds to Wistar Rattus. By establishing a cDNA library of miRNA from rat muscle tumor tissue induced by Ni3S2, we found that the expression of miR-222 was significantly upregulated in tumor tissue compared with the normal tissue. As we expected, the expression levels of target genes of miR-222, CDKN1B and CDKN1C, were downregulated in the nickel-induced tumor. The same alteration of miR-222 and its target genes was also found in malignant 16HBE cells induced with Ni3S2 compounds. We conclude that miR-222 may promote cell proliferation infinitely during nickel-induced tumorigenesis in part by regulating the expression of its target genes CDKN1B and CDKN1C. Our study elucidated a novel molecular mechanism of nickel-induced tumorigenesis. 相似文献
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859.
Guofen Gao Lindsay Wieczorek Kristina K. Peachman Victoria R. Polonis Carl R. Alving Mangala Rao Venigalla B. Rao 《The Journal of biological chemistry》2013,288(1):234-246
The HIV-1 envelope spike is a trimer of heterodimers composed of an external glycoprotein gp120 and a transmembrane glycoprotein gp41. gp120 initiates virus entry by binding to host receptors, whereas gp41 mediates fusion between viral and host membranes. Although the basic pathway of HIV-1 entry has been extensively studied, the detailed mechanism is still poorly understood. Design of gp41 recombinants that mimic key intermediates is essential to elucidate the mechanism as well as to develop potent therapeutics and vaccines. Here, using molecular genetics and biochemical approaches, a series of hypotheses was tested to overcome the extreme hydrophobicity of HIV-1 gp41 and design a soluble near full-length gp41 trimer. The two long heptad repeat helices HR1 and HR2 of gp41 ectodomain were mutated to disrupt intramolecular HR1-HR2 interactions but not intermolecular HR1-HR1 interactions. This resulted in reduced aggregation and improved solubility. Attachment of a 27-amino acid foldon at the C terminus and slow refolding channeled gp41 into trimers. The trimers appear to be stabilized in a prehairpin-like structure, as evident from binding of a HR2 peptide to exposed HR1 grooves, lack of binding to hexa-helical bundle-specific NC-1 mAb, and inhibition of virus neutralization by broadly neutralizing antibodies 2F5 and 4E10. Fusion to T4 small outer capsid protein, Soc, allowed display of gp41 trimers on the phage nanoparticle. These approaches for the first time led to the design of a soluble gp41 trimer containing both the fusion peptide and the cytoplasmic domain, providing insights into the mechanism of entry and development of gp41-based HIV-1 vaccines. 相似文献
860.
Heng Zhang Heng Zhang Zeng-Qiang Gao Wen-Jia Wang Guang-Feng Liu Jian-Hua Xu Xiao-Dong Su Yu-Hui Dong 《The Journal of biological chemistry》2013,288(8):5928-5939
The type VI secretion system (T6SS), a multisubunit needle-like apparatus, has recently
been found to play a role in interspecies interactions. The Gram-negative bacteria
harboring T6SS (donor) deliver the effectors into their neighboring cells (recipient) to
kill them. Meanwhile, the cognate immunity proteins were employed to protect the donor
cells against the toxic effectors. Tae4 (type VI
amidase effector 4) and Tai4
(type VI amidase
immunity 4) are newly identified T6SS effector-immunity pairs.
Here, we report the crystal structures of Tae4 from Enterobacter cloacae
and Tae4-Tai4 complexes from both E. cloacae and Salmonella
typhimurium. Tae4 acts as a dl-endopeptidase and displays a typical
N1pC/P60 domain. Unlike Tsi1 (type VI
secretion immunity 1), Tai4 is an
all-helical protein and forms a dimer in solution. The small angle x-ray scattering study
combined with the analytical ultracentrifugation reveal that the Tae4-Tai4 complex is a
compact heterotetramer that consists of a Tai4 dimer and two Tae4 molecules in solution.
Structure-based mutational analysis of the Tae4-Tai4 interface shows that a helix
(α3) of one subunit in dimeric Tai4 plays a major role in binding of Tae4, whereas
a protruding loop (L4) in the other subunit is mainly responsible for inhibiting Tae4
activity. The inhibition process requires collaboration between the Tai4 dimer. These
results reveal a novel and unique inhibition mechanism in effector-immunity pairs and
suggest a new strategy to develop antipathogen drugs. 相似文献