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991.
Fabian P McDevitt JJ DeHaan WH Fung RO Cowling BJ Chan KH Leung GM Milton DK 《PloS one》2008,3(7):e2691
Background
Recent studies suggest that humans exhale fine particles during tidal breathing but little is known of their composition, particularly during infection.Methodology/Principal Findings
We conducted a study of influenza infected patients to characterize influenza virus and particle concentrations in their exhaled breath. Patients presenting with influenza-like-illness, confirmed influenza A or B virus by rapid test, and onset within 3 days were recruited at three clinics in Hong Kong, China. We collected exhaled breath from each subject onto Teflon filters and measured exhaled particle concentrations using an optical particle counter. Filters were analyzed for influenza A and B viruses by quantitative polymerase chain reaction (qPCR). Twelve out of thirteen rapid test positive patients provided exhaled breath filter samples (7 subjects infected with influenza B virus and 5 subjects infected with influenza A virus). We detected influenza virus RNA in the exhaled breath of 4 (33%) subjects–three (60%) of the five patients infected with influenza A virus and one (14%) of the seven infected with influenza B virus. Exhaled influenza virus RNA generation rates ranged from <3.2 to 20 influenza virus RNA particles per minute. Over 87% of particles exhaled were under 1 µm in diameter.Conclusions
These findings regarding influenza virus RNA suggest that influenza virus may be contained in fine particles generated during tidal breathing, and add to the body of literature suggesting that fine particle aerosols may play a role in influenza transmission. 相似文献992.
Adam S. Olia Yaroslav Tsybovsky Steven J. Chen Cuiping Liu Alexandra F. Nazzari Li Ou Lingshu Wang Wing-Pui Kong Kwan Leung Tracy Liu Tyler Stephens I-Ting Teng Shuishu Wang Eun Sung Yang Baoshan Zhang Yi Zhang Tongqing Zhou John R. Mascola Peter D. Kwong 《The Journal of biological chemistry》2021,297(4)
The SARS-CoV-2 spike is the primary target of virus-neutralizing antibodies and critical to the development of effective vaccines against COVID-19. Here, we demonstrate that the prefusion-stabilized two-proline “S2P” spike—widely employed for laboratory work and clinical studies—unfolds when stored at 4 °C, physiological pH, as observed by electron microscopy (EM) and differential scanning calorimetry, but that its trimeric, native-like conformation can be reacquired by low pH treatment. When stored for approximately 1 week, this unfolding does not significantly alter antigenic characteristics; however, longer storage diminishes antibody binding, and month-old spike elicits virtually no neutralization in mice despite inducing high ELISA-binding titers. Cryo-EM structures reveal the folded fraction of spike to decrease with aging; however, its structure remains largely similar, although with varying mobility of the receptor-binding domain. Thus, the SARS-CoV-2 spike is susceptible to unfolding, which affects immunogenicity, highlighting the need to monitor its integrity. 相似文献
993.
Ophioceras guttulatum sp. nov.,O. hongkongense sp. nov. andO. palmae sp. nov. are described and illustrated from decaying terrestrial palms and woody substrates in freshwater habitats. They
all have black perithecia with long necks, cylindrical asci with refractive apical rings and filiform ascospores. 相似文献
994.
Models have been well developed describing human movements as vectors of the spread of non-indigenous species (NIS). However, to be maximally useful, predictions need to be integrated with management models of how different policies change human behaviour and lead to concurrent changes in invasion risk. Using the dispersal of freshwater organisms by recreational boaters as our study system and mandatory boat washing as our management strategy, we conducted a survey of recreational boaters (n = 580 respondents, t = 2354 boating trips) in Ontario, Canada, and performed counterfactual analysis of boater behavior across different management options. We developed a model to quantify three responses to mandatory boat washing policies: (1) the continued use of a policy lake; (2) switching to a non-policy lake (“trip redistribution”); or, (3) a reduction in boating trips (“trip loss”). We found that boater and locational traits did not have a significant effect, but even modest user fees at washing stations greatly influenced trip redistribution and loss, explaining 87% of the variation in boater choices. These results indicate that user fees can strongly reduce the effectiveness of boat washing programs to mitigate invasion risk and could have unintended local economic effects, supporting the need to minimize boater expense as a program goal. In contrast, only minor redistribution and loss occurred if users washed but did not pay, and when taken together with the lack of effect for boater and locational traits, suggest that simple human-mediated dispersal models would be sufficient to prioritize management actions under “zero fee” scenarios. Simulating management scenarios using an existing spread model for 10 aquatic NIS in Ontario further emphasized the benefit of zero fees. Although averted invasions increased monotonically with effort (number of lakes with washing stations), the relative effectiveness (number of invasions averted per unit effort) was high even with management of a single lake, given zero fees, but required washing stations at far more lakes to maximize relative effectiveness when user fees were imposed. 相似文献
995.
996.
Renjie Huang Daniel M. Ayine-Tora M. Nasri Muhammad Rosdi Yu Li Jóhannes Reynisson Ivanhoe K.H. Leung 《Bioorganic & medicinal chemistry letters》2017,27(2):277-281
Heat shock protein 90 (HSP90) is a molecular chaperone that plays important functional roles in cells. The chaperone activity of HSP90 is regulated by the hydrolysis of ATP at the protein’s N-terminal domain. HSP90, in particular the N-terminal domain, is a current inhibition target for therapeutic treatments of cancers. This paper describes an application of virtual screening, thermal shift assaying and protein NMR spectroscopy leading to the discovery of HSP90 inhibitors that contain the resorcinol structure. The resorcinol scaffold can be found in a class of HSP90 inhibitors that are currently undergoing clinical trials. The proved success of the resorcinol moiety in HSP90 inhibitors validates this combined virtual screen and biophysical technique approach, which may be applied for future inhibitor discovery work for HSP90 as well as other targets. 相似文献
997.
Hung-Hsing Chao Po-Yuan Chen Wen-Rui Hao Wei-Ping Chiang Tzu-Hurng Cheng Shih-Hurng Loh Yuk-Man Leung Ju-Chi Liu Jin-Jer Chen Li-Chin Sung 《Journal of biomedical science》2017,24(1):85
Background
This study investigated whether lipopolysaccharide (LPS) increase protease-activated receptor-2 (PAR-2) expression and enhance the association between PAR-2 expression and chemokine production in human vascular endothelial cells (ECs).Methods
The morphology of ECs was observed through microphotography in cultured human umbilical vein ECs (EA. hy926 cells) treated with various LPS concentrations (0, 0.25, 0.5, 1, and 2 μg/mL) for 24 h, and cell viability was assessed using the MTT assay. Intracellular calcium imaging was performed to assess agonist (trypsin)-induced PAR-2 activity. Western blotting was used to explore the LPS-mediated signal transduction pathway and the expression of PAR-2 and adhesion molecule monocyte chemoattractant protein-1 (MCP-1) in ECs.Results
Trypsin stimulation increased intracellular calcium release in ECs. The calcium influx was augmented in cells pretreated with a high LPS concentration (1 μg/mL). After 24 h treatment of LPS, no changes in ECs viability or morphology were observed. Western blotting revealed that LPS increased PAR-2 expression and enhanced trypsin-induced extracellular signal-regulated kinase (ERK)/p38 phosphorylation and MCP-1 secretion. However, pretreatment with selective ERK (PD98059), p38 mitogen-activated protein kinase (MAPK) (SB203580) inhibitors, and the selective PAR-2 antagonist (FSLLRY-NH2) blocked the effects of LPS-activated PAR-2 on MCP-1 secretion.Conclusions
Our findings provide the first evidence that the bacterial endotoxin LPS potentiates calcium mobilization and ERK/p38 MAPK pathway activation and leads to the secretion of the pro-inflammatory chemokine MCP-1 by inducing PAR-2 expression and its associated activity in vascular ECs. Therefore, PAR-2 exerts vascular inflammatory effects and plays an important role in bacterial infection-induced pathological responses.998.
Duo Wai-Chi Wong Yan Wang Tony Lin-Wei Chen Aaron Kam-Lun Leung 《Computer methods in biomechanics and biomedical engineering》2017,20(14):1525-1532
Subtalar joint arthroereisis (SJA) has been introduced to control the hyperpronation in cases of flatfoot. The objective of this study is to evaluate the biomechanical consequence of SJA to restore the internal stress and load transfer to the intact state from the attenuated biomechanical condition induced by posterior tibial tendon dysfunction (PTTD). A three-dimensional finite element model of the foot and ankle complex was constructed based on clinical images of a healthy female (age 28 years, height 165 cm, body mass 54 kg). The boundary and loading condition during walking was acquired from the gait experiment of the model subject. Five sets of simulations (conditions) were completed: intact condition, mild PTTD, severe PTTD, mild PTTD with SJA, severe PTTD with SJA. The maximum von Mises stress of the metatarsal shafts and the load transfer along the midfoot during stance were analyzed. Generally, SJA deteriorated the joint force of the medial cuneonavicular and calcaneocuboid joints during late stance, while that of the metatarsocuneiform joints during early stance were over-corrected. Only the calcaneocuboid joint force at 45% stance demonstrated a trend of improvement. Besides, SJA exaggerated the increased stress of the metatarsals compared to the PTTD conditions, except that of the first metatarsal. Our study did not support the hypothesis that SJA can restore the internal load transfer and midfoot stress. SJA cannot compensate the salvage of midfoot stability attributed by PTTD and could be biomechanically insufficient to restore the biomechanical environment. Additional procedures such as orthotic intervention may be necessary. 相似文献
999.
Decreased IL-15 may contribute to elevated IgE and acute inflammation in atopic dermatitis. 总被引:2,自引:0,他引:2
Peck Y Ong Qutayba A Hamid Jeffrey B Travers Ian Strickland Muhamed Al Kerithy Mark Boguniewicz Donald Y M Leung 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(1):505-510
PBMC and acute skin lesions of patients with atopic dermatitis (AD) are characterized by increased IL-4 and IL-13, but decreased IFN-gamma production. This bias toward an increased Th2 cytokine profile may contribute to the elevated IgE levels and acute skin inflammation seen in AD. In this study, we examined the levels of IL-15, a Th1-like cytokine, in the PBMC and the skin lesions of AD patients. IL-15 secretion by Staphylococcal enterotoxin B-treated PBMC of AD patients was significantly lower than that of normals and psoriasis patients (p < 0.001). Membrane-bound IL-15 expression as measured by mean fluorescence intensity and percentage of IL-15-positive cells in Staphylococcal enterotoxin B-treated monocytes of AD patients (644 +/- 49% and 12.7 +/- 0.6%, respectively) were significantly lower than that of normals (869 +/- 56% and 15.8 +/- 1.2%, respectively) and psoriasis patients (1488 +/- 217% and 22.7 +/- 0.8%, respectively; p < 0.0007 and p < 0.0001, respectively). The membrane-bound IL-15 expression was also significantly lower in the control monocytes of AD patients compared with that in normals and psoriasis patients. There was no significant difference in the absolute number or percentage of monocytes between the study subjects. However, psoriasis skin lesions were found to have significantly more IL-15 mRNA-expressing cells (22.4 +/- 1.7) compared with that in acute AD (7.5 +/- 1.7) and chronic AD (13.7 +/- 1.7) skin lesions (p < 0.05). IL-15 enhanced IFN-gamma production by the PBMC of AD patients (p < 0.01), but not by that of normal individuals or psoriasis patients. In addition, IL-15 was found to suppress IgE synthesis (p < 0.01) by the PBMC of AD patients. These data support the concept that reduced IL-15 expression may contribute to the pathogenesis of AD. 相似文献
1000.