全文获取类型
收费全文 | 1597篇 |
免费 | 112篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 13篇 |
2021年 | 17篇 |
2020年 | 14篇 |
2019年 | 11篇 |
2018年 | 23篇 |
2017年 | 22篇 |
2016年 | 27篇 |
2015年 | 59篇 |
2014年 | 54篇 |
2013年 | 109篇 |
2012年 | 113篇 |
2011年 | 112篇 |
2010年 | 68篇 |
2009年 | 55篇 |
2008年 | 90篇 |
2007年 | 98篇 |
2006年 | 90篇 |
2005年 | 87篇 |
2004年 | 71篇 |
2003年 | 64篇 |
2002年 | 66篇 |
2001年 | 25篇 |
2000年 | 33篇 |
1999年 | 36篇 |
1998年 | 20篇 |
1997年 | 12篇 |
1996年 | 12篇 |
1995年 | 9篇 |
1994年 | 11篇 |
1993年 | 10篇 |
1992年 | 26篇 |
1991年 | 19篇 |
1990年 | 18篇 |
1989年 | 19篇 |
1988年 | 16篇 |
1987年 | 17篇 |
1986年 | 17篇 |
1985年 | 16篇 |
1984年 | 14篇 |
1983年 | 11篇 |
1982年 | 14篇 |
1980年 | 8篇 |
1979年 | 9篇 |
1978年 | 9篇 |
1977年 | 11篇 |
1976年 | 8篇 |
1975年 | 7篇 |
1974年 | 5篇 |
1973年 | 5篇 |
排序方式: 共有1710条查询结果,搜索用时 15 毫秒
1.
Susan Morrison Grace John-Stewart John J. Egessa Sezi Mubezi Sylvia Kusemererwa Dennis K. Bii Nulu Bulya Francis Mugume James D. Campbell Jonathan Wangisi Elizabeth A. Bukusi Connie Celum Jared M. Baeten Partners PrEP Study Team 《PloS one》2015,10(10)
During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting. 相似文献
2.
Xiao-Xiao Li Bun Tsoi Yi-Fang Li Hiroshi Kurihara Rong-Rong He 《The journal of histochemistry and cytochemistry》2015,63(5):301-311
Cardiolipin (CL) is a unique dimeric phospholipid that exists almost exclusively in the inner mitochondrial membrane (IMM) in eukaryotic cells. Two chiral carbons and four fatty acyl chains in CL result in a flexible body allowing interactions with respiratory chain complexes and mitochondrial substrate carriers. Due to its high content of unsaturated fatty acids, CL is particularly prone to reactive oxygen species (ROS)-induced oxidative attacks. Under mild mitochondrial damage, CL is redistributed to the outer mitochondrial membrane (OMM) and serves as a recognition signal for dysfunctional mitochondria, which are rapidly sequestered by autophagosomes. However, peroxidation of CL is far greater in response to severe stress than under normal or mild-damage conditions. The accumulation of oxidized CL on the OMM results in recruitment of Bax and formation of the mitochondrial permeability transition pore (MPTP), which releases Cytochrome c (Cyt c) from mitochondria. Over the past decade, the significance of CL in the function of mitochondrial bioenergy has been explored. Moreover, approaches to analyzing CL have become more effective and accurate. In this review, we discuss the unique structural features of CL as well as the current understanding of CL-based molecular mechanisms of mitophagy and apoptosis. 相似文献
3.
Paul McDonough D Merrill Dane Connie C W Hsia Cuneyt Yilmaz Robert L Johnson 《Journal of applied physiology》2006,100(2):474-481
In a previous study, our laboratory showed that young dogs born at sea level (SL) and raised from 2.5 mo of age to beyond somatic maturity at a high altitude (HA) of 3,100 m show enhanced resting lung function (Johnson RL Jr, Cassidy SS, Grover RF, Schutte JE, and Epstein RH. J Appl Physiol 59: 1773-1782, 1985). To examine whether HA-induced adaptation improves pulmonary gas exchange during exercise and whether adaptation is reversible when animals return to SL before somatic maturity, we raised 2.5-mo-old foxhounds at HA (3,800 m) for 5 mo (to age 7.5 mo) before returning them to SL. Lung function was measured under anesthesia 1 mo and 2 yr after return to SL and during exercise approximately 1 yr after return. In animals exposed to HA relative to simultaneous litter-matched SL controls, resting circulating blood and erythrocyte volumes, lung volumes, septal volume estimated by a rebreathing technique, and lung tissue volume estimated by high-resolution computed tomography scan were persistently higher. Lung diffusing capacity, membrane diffusing capacity, and pulmonary capillary blood volume estimated at a given cardiac output were significantly higher in animals exposed to HA, whereas maximal oxygen uptake and hematocrit were similar between groups. We conclude that relatively short exposure to HA during somatic maturation improves long-term lung function into adulthood. 相似文献
4.
Joanne K. Gardner Cyril D. S. Mamotte Priya Patel Teong Ling Yeoh Connie Jackaman Delia J. Nelson 《PloS one》2015,10(4)
Dendritic cells (DCs) play an important role in the generation of anti-cancer immune responses, however there is evidence that DCs in cancer patients are dysfunctional. Lipid accumulation driven by tumor-derived factors has recently been shown to contribute to DC dysfunction in several human cancers, but has not yet been examined in mesothelioma. This study investigated if mesothelioma tumor cells and/or their secreted factors promote increases in DC lipid content and modulate DC function. Human monocyte-derived DCs (MoDCs) were exposed to human mesothelioma tumor cells and tumor-derived factors in the presence or absence of lipoproteins. The data showed that immature MoDCs exposed to mesothelioma cells or factors contained increased lipid levels relative to control DCs. Lipid accumulation was associated with reduced antigen processing ability (measured using a DQ OVA assay), upregulation of the co-stimulatory molecule, CD86, and production of the tolerogenic cytokine, IL-10. Increases in DC lipid content were further enhanced by co-exposure to mesothelioma-derived factors and triglyceride-rich lipoproteins, but not low-density lipoproteins. In vivo studies using a murine mesothelioma model showed that the lipid content of tumor-infiltrating CD4+CD8α- DCs, CD4-CD8α- DCs DCs and plasmacytoid DCs increased with tumor progression. Moreover, increasing tumor burden was associated with reduced proliferation of tumor-antigen-specific CD8+ T cells in tumor-draining lymph nodes. This study shows that mesothelioma promotes DC lipid acquisition, which is associated with altered activation status and reduced capacity to process and present antigens, which may impair the ability of DCs to generate effective anti mesothelioma T cell responses. 相似文献
5.
6.
Fibroblast cells from two Japanese patients with Bloom's syndrome (BS) and normal donors were studied for the inactivation of colony-forming ability and the induction of sister-chromatid exchanges (SCEs) after N-ethyl-N-nitrosourea (ENU) treatment. The reduction of ENU-induced SCEs as a function of post-treatment incubation time was also compared between BS and normal fibroblasts. BS cells were approximately 4 times more sensitive than normal cells to the lethal effect of ENU and remarkably hypersensitive to the SCE induction by ENU. The post-treatment incubation of ENU-treated normal cells in the fresh medium resulted in a time-dependent decrease of the SCE level until 6 h after which time the SCE level remained the plateau of about 50% of the initial level. In contrast, the ENU-induced SCEs in BS cells decreased much more slowly with post-treatment incubation time and its half life was 24 h. These results collectively support the view that BS cells may be defective in the rapid repair of certain type(s) of DNA damages induced by ENU. 相似文献
7.
Sister-chromatid exchanges induced by ultraviolet light in Bloom's syndrome fibroblasts 总被引:1,自引:0,他引:1
The relationships between the cytotoxic effect of ultraviolet light and the UV-induced sister-chromatid exchanges (SCEs) were compared among fibroblast cell strains from two unrelated Bloom's syndrome (BS) patients, one xeroderma pigmentosum (XP) patient belonging to complementation group A and two unrelated normal controls. The "net" induced SCEs as a function of UV fluence, obtained by subtracting spontaneous SCEs from observed SCEs, were much higher in both BS cells and XP group A cells than in normal cells. The relative efficiency of induced SCE, defined as the "net" induced SCEs as a function of surviving fraction after UV irradiation, was higher in BS cells than in normal and XP cells, and there was essentially no difference between XP and normal cells. These results imply that in addition to the extremely high frequency of spontaneous SCEs, the increased efficiency in UV induction of SCEs may reflect the intrinsic defect(s) in BS cells. 相似文献
8.
cDNA cloning and amino acid sequence of bovine brain 2',3'-cyclic-nucleotide 3'-phosphodiesterase 总被引:4,自引:0,他引:4
2',3'-Cyclic-nucleotide 3'-phosphodiesterase (EC 3.1.4.37) has been widely used as a marker for myelin-oligodendrocytes in the central nervous system. Evidence has been provided that the enzyme is identical with one of the Wolfgram proteins of central nervous system myelin. The amino acid sequence of bovine 2',3'-cyclic-nucleotide 3'-phosphodiesterase was determined by both protein and cDNA sequence analyses. Protein sequence analysis was done on bovine elastase 2',3'-cyclic-nucleotide 3'-phosphodiesterase, a low molecular weight enzyme obtained by solubilization with pancreatic elastase (EC 3.4.21.36) (Nishizawa, Y., Kurihara, T., and Takahashi, Y. (1980) Biochem. J. 191, 71-82; Kurihara, T., Nishizawa, Y., Takahashi, Y., and Odani, S. (1981) Biochem. J. 195, 153-157). Based on the carboxyl-terminal sequence of bovine elastase 2',3'-cyclic-nucleotide 3'-phosphodiesterase, synthetic oligodeoxyribonucleotides were prepared and used as probes for screening a cDNA library of bovine brain. A cDNA of 2305 base pairs was obtained and sequenced, and the complete amino acid sequence of bovine 2',3'-cyclic-nucleotide 3'-phosphodiesterase was deduced. Bovine 2',3'-cyclic-nucleotide 3'-phosphodiesterase deduced contains 400 amino acids including initiation methionine and has a molecular weight of 44,850. Bovine elastase 2',3'-cyclic-nucleotide 3'-phosphodiesterase corresponds to the 236 amino acids of bovine 2',3'-cyclic-nucleotide 3'-phosphodiesterase. RNA blot analysis revealed a single-species mRNA of about 2600 bases. 相似文献
9.
Y Hakeda Y Nakatani T Yoshino N Kurihara K Fujita N Maeda M Kumegawa 《Journal of biochemistry》1987,101(6):1463-1469
The effect of forskolin on collagen production in osteoblasts was investigated by using clonal osteoblastic MC3T3-E1 cells cultured in a-minimum essential medium containing 0.1% bovine serum albumin. Forskolin increased the adenylate cyclase activity in membranes pelleted from homogenates of the cell line in a dose-dependent manner. The drug caused a 13-fold stimulation at 10(-4) M, indicating that the compound directly acts on adenylate cyclase, leading to an increase in the intracellular cAMP content of the cells. Collagen accumulation in the cultures was elevated by one-day treatment with 5 X 10(-5) M forskolin to about twice that in the controls. The stimulation was mainly due to an elevation in collagen synthesis but not to an inhibition of intracellular collagen degradation because forskolin dose-dependently increased collagen synthesis; it also significantly increased the amount of low-molecular-weight hydroxyproline found in the cultures. Cells treated with forskolin produced mainly type I collagen, as found in bone matrix in situ, with only small amounts of other types of collagen. Furthermore, forskolin time-dependently inhibited DNA synthesis in the cells, indicating that the increase in type I collagen synthesis by forskolin was not due to stimulated cell proliferation. These results suggest that cAMP is closely linked to the differentiation of osteoblasts in vitro. 相似文献
10.