全文获取类型
收费全文 | 1864篇 |
免费 | 186篇 |
出版年
2023年 | 11篇 |
2022年 | 9篇 |
2021年 | 38篇 |
2020年 | 24篇 |
2019年 | 29篇 |
2018年 | 40篇 |
2017年 | 40篇 |
2016年 | 64篇 |
2015年 | 123篇 |
2014年 | 108篇 |
2013年 | 153篇 |
2012年 | 190篇 |
2011年 | 172篇 |
2010年 | 105篇 |
2009年 | 113篇 |
2008年 | 134篇 |
2007年 | 134篇 |
2006年 | 105篇 |
2005年 | 96篇 |
2004年 | 84篇 |
2003年 | 62篇 |
2002年 | 57篇 |
2001年 | 15篇 |
2000年 | 4篇 |
1999年 | 24篇 |
1998年 | 18篇 |
1997年 | 12篇 |
1996年 | 9篇 |
1995年 | 11篇 |
1994年 | 7篇 |
1993年 | 8篇 |
1992年 | 3篇 |
1991年 | 9篇 |
1989年 | 8篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 4篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 4篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1965年 | 1篇 |
1962年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有2050条查询结果,搜索用时 15 毫秒
931.
Alvin Aaden Yim-Hol Chan Paulina Giraldo-Perez Sonja Smith Daniel T. Blumstein 《Biology letters》2010,6(4):458-461
Many studies have focused on the effects of anthropogenic noise on animal communication, but only a few have looked at its effect on other behavioural systems. We designed a playback experiment to test the effect of noise on predation risk assessment. We found that in response to boat motor playback, Caribbean hermit crabs (Coenobita clypeatus) allowed a simulated predator to approach closer before they hid. Two hypotheses may explain how boat noise affected risk assessment: it masked an approaching predator''s sound; and/or it reallocated some of the crabs'' finite attention, effectively distracting them, and thus preventing them from responding to an approaching threat. We found no support for the first hypothesis: a silent looming object still got closer during boat motor playbacks than during silence. However, we found support for the attentional hypothesis: when we added flashing lights to the boat motor noise to further distract the hermit crabs, we were able to approach the crabs more closely than with the noise alone. Anthropogenic sounds may thus distract prey and make them more vulnerable to predation. 相似文献
932.
Background
Hydrogen sulphide (H2S) is a gaseous neuro-mediator that exerts analgesic effects in rodent models of visceral pain by activating KATP channels. A body of evidence support the notion that KATP channels interact with endogenous opioids. Whether H2S-induced analgesia involves opioid receptors is unknown.Methods
The perception of painful sensation induced by colorectal distension (CRD) in conscious rats was measured by assessing the abdominal withdrawal reflex. The contribution of opioid receptors to H2S-induced analgesia was investigated by administering rats with selective μ, κ and δ opioid receptor antagonists and antisenses. To investigate whether H2S causes μ opioid receptor (MOR) transactivation, the neuronal like cells SKNMCs were challenged with H2S in the presence of MOR agonist (DAMGO) or antagonist (CTAP). MOR activation and phosphorylation, its association to β arrestin and internalization were measured.Results
H2S exerted a potent analgesic effects on CRD-induced pain. H2S-induced analgesia required the activation of the opioid system. By pharmacological and molecular analyses, a robust inhibition of H2S-induced analgesia was observed in response to central administration of CTAP and MOR antisense, while κ and δ receptors were less involved. H2S caused MOR transactivation and internalization in SKNMCs by a mechanism that required AKT phosphorylation. MOR transactivation was inhibited by LY294002, a PI3K inhibitor, and glibenclamide, a KATP channels blocker.Conclusions
This study provides pharmacological and molecular evidence that antinociception exerted by H2S in a rodent model of visceral pain is modulated by the transactivation of MOR. This observation provides support for development of new pharmacological approaches to visceral pain. 相似文献933.
Florian J. Lippl Sonja Neubauer Susanne Schipfer Nicole Lichter Amanda Tufman Bärbel Otto Rainald Fischer 《Obesity (Silver Spring, Md.)》2010,18(4):675-681
The reason for weight loss at high altitudes is largely unknown. To date, studies have been unable to differentiate between weight loss due to hypobaric hypoxia and that related to increased physical exercise. The aim of our study was to examine the effect of hypobaric hypoxia on body weight at high altitude in obese subjects. We investigated 20 male obese subjects (age 55.7 ± 4.1 years, BMI 33.7 ± 1.0 kg/m2). Body weight, waist circumference, basal metabolic rate (BMR), nutrition protocols, and objective activity parameters as well as metabolic and cardiovascular parameters, blood gas analysis, leptin, and ghrelin were determined at low altitude (LA) (Munich 530 m, D1), at the beginning and at the end of a 1‐week stay at high altitude (2,650 m, D7 and D14) and 4 weeks after returning to LA (D42). Although daily pace counting remained stable at high altitude, at D14 and D42, participants weighed significantly less and had higher BMRs than at D1. Food intake was decreased at D7. Basal leptin levels increased significantly at high altitude despite the reduction in body weight. Diastolic blood pressure was significantly lower at D7, D14, and D42 compared to D1. This study shows that obese subjects lose weight at high altitudes. This may be due to a higher metabolic rate and reduced food intake. Interestingly, leptin levels rise in high altitude despite reduced body weight. Hypobaric hypoxia seems to play a major role, although the physiological mechanisms remain unclear. Weight loss at high altitudes was associated with clinically relevant improvements in diastolic blood pressure. 相似文献
934.
Kajula M Tejesvi MV Kolehmainen S Mäkinen A Hokkanen J Mattila S Pirttilä AM 《Fungal biology》2010,114(2-3):248-254
Production of extracellular siderophores is typical for many plant-associated microbes, both mutualistic and antagonistic. Various strains of mycorrhizal fungi produce siderophores, and siderophore production by pathogenic fungi is typically associated with virulence. We analyzed extracellular siderophore production along with production of antibacterial and antioxidant compounds in foliar endophytic fungi of Scots pine (Pinus sylvestris L.) and Labrador tea (Rhododendron tomentosum Harmaja). The siderophore produced in vitro was ferricrocin, quantities ranging between 7.9 and 17.6 μg/l. Only the fungi with antibacterial activity produced ferricrocin and any well-known siderophores were not detected in the broths of antioxidant-producing fungi. Therefore, production of ferricrocin is typical for some, but not all foliar endophytic fungi. Ferricrocin was detected in the leaves of Labrador tea, which suggests that ferricrocin may play a role in vivo in the interaction between the endophyte and plant host. 相似文献
935.
Enmoore Lin Benson Kiniboro Laurie Gray Stuart Dobbie Leanne Robinson Annemarie Laumaea Sonja Sch?pflin Danielle Stanisic Inoni Betuela Melinda Blood-Zikursh Peter Siba Ingrid Felger Louis Schofield Peter Zimmerman Ivo Mueller 《PloS one》2010,5(2)
Background
Where P. vivax and P. falciparum occur in the same population, the peak burden of P. vivax infection and illness is often concentrated in younger age groups. Experiences from malaria therapy patients indicate that immunity is acquired faster to P. vivax than to P. falciparum challenge. There is however little prospective data on the comparative risk of infection and disease from both species in young children living in co-endemic areas.Methodology/Principal Findings
A cohort of 264 Papua New Guinean children aged 1-3 years (at enrolment) were actively followed-up for Plasmodium infection and febrile illness for 16 months. Infection status was determined by light microscopy and PCR every 8 weeks and at each febrile episode. A generalised estimating equation (GEE) approach was used to analyse both prevalence of infection and incidence of clinical episodes. A more pronounced rise in prevalence of P. falciparum compared to P. vivax infection was evident with increasing age. Although the overall incidence of clinical episodes was comparable (P. falciparum: 2.56, P. vivax 2.46 episodes / child / yr), P. falciparum and P. vivax infectious episodes showed strong but opposing age trends: P. falciparum incidence increased until the age of 30 months with little change thereafter, but incidence of P. vivax decreased significantly with age throughout the entire age range. For P. falciparum, both prevalence and incidence of P. falciparum showed marked seasonality, whereas only P. vivax incidence but not prevalence decreased in the dry season.Conclusions/Significance
Under high, perennial exposure, children in PNG begin acquiring significant clinical immunity, characterized by an increasing ability to control parasite densities below the pyrogenic threshold to P. vivax, but not to P. falciparum, in the 2nd and 3rd year of life. The ability to relapse from long-lasting liver-stages restricts the seasonal variation in prevalence of P. vivax infections. 相似文献936.
Xuhua Guan Benjamin J. Silk Wenkai Li Aaron T. Fleischauer Xuesen Xing Xiaoqing Jiang Hongjie Yu Sonja J. Olsen Adam L. Cohen 《PloS one》2010,5(7)
Background
Pneumonia is a leading infectious disease killer worldwide, yet the burden in China is not well understood as much of the data is published in the non-English literature.Methodology/Principal Findings
We systematically reviewed the Chinese- and English-language literature for studies with primary data on pneumonia incidence and mortality in mainland China. Between 1985 and 2008, 37 studies met the inclusion criteria. The quality of the studies was highly variable. For children <5 years, incidence ranged from 0.06–0.27 episodes per person-year and mortality ranged from 184–1,223 deaths per 100,000 population. Overall incidence and mortality were stable or decreased over the study period and were higher in rural compared to urban areas.Conclusions/Significance
Pneumonia continues to be a major public health challenge in young children in China, and estimates of pneumonia incidence and mortality vary widely. Reliable surveillance data and new prevention efforts may be needed to achieve and document additional declines, especially in areas with higher incidence and mortality such as rural settings. 相似文献937.
Stasyk T Holzmann J Stumberger S Ebner HL Hess MW Bonn GK Mechtler K Huber LA 《Proteomics》2010,10(22):4117-4127
The p14/MP1 scaffold complex binds MEK1 and ERK1/2 on late endosomes, thus regulating the strength, duration and intracellular location of MAPK signaling. By organelle proteomics we have compared the protein composition of endosomes purified from genetically modified p14?/?, p14+/? and p14(rev) mouse embryonic fibroblasts. The latter ones were reconstituted retrovirally from p14?/? mouse embryonic fibroblasts by reexpression of pEGFP-p14 at equimolar ratios with its physiological binding partner MP1, as shown here by absolute quantification of MP1 and p14 proteins on endosomes by quantitative MS using the Equimolarity through Equalizer Peptide strategy. A combination of subcellular fractionation, 2-D DIGE and MALDI-TOF/TOF MS revealed 31 proteins differentially regulated in p14?/? organelles, which were rescued by reexpression of pEGFP-p14 in p14?/? endosomes. Regulated proteins are known to be involved in actin remodeling, endosomal signal transduction and trafficking. Identified proteins and their in silico interaction networks suggested that endosomal signaling might regulate such major cellular functions such as proliferation, differentiation, migration and survival. 相似文献
938.
939.
Strang-Karlsson S Kajantie E Pesonen AK Räikkönen K Hovi P Lahti J Heinonen K Järvenpää AL Eriksson JG Andersson S Paavonen EJ 《Chronobiology international》2010,27(9-10):1829-1842
The authors explored morningness-eveningness propensity in adults born prematurely at very low birth weight (VLBW; 1500g) and in controls born at term. At age 21 to 29 yrs, 184 participants completed the Morningness-Eveningness Questionnaire (MEQ). Compared with controls, VLBW adults scored higher in morningness propensity (group difference: 2.8 scores, 95% confidence interval: 0.1 to 5.5; p?=?.042). This finding was confined to those VLBW adults whose birth weight was not small for gestational age, and remained similar when adjusting for age, sex, and working conditions. The finding is potentially important, since morningness is associated with beneficial health outcomes. 相似文献
940.
Nilofer Husain Karolina L. Tkaczuk Shenoy Rajesh Tulsidas Katarzyna H. Kaminska Sonja ?ubrilo Gordana Maravi?-Vlahovi?ek Janusz M. Bujnicki J. Sivaraman 《Nucleic acids research》2010,38(12):4120-4132
Sgm (Sisomicin-gentamicin methyltransferase) from antibiotic-producing bacterium Micromonospora zionensis is an enzyme that confers resistance to aminoglycosides like gentamicin and sisomicin by specifically methylating G1405 in bacterial 16S rRNA. Sgm belongs to the aminoglycoside resistance methyltransferase (Arm) family of enzymes that have been recently found to spread by horizontal gene transfer among disease-causing bacteria. Structural characterization of Arm enzymes is the key to understand their mechanism of action and to develop inhibitors that would block their activity. Here we report the structure of Sgm in complex with cofactors S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) at 2.0 and 2.1 Å resolution, respectively, and results of mutagenesis and rRNA footprinting, and protein-substrate docking. We propose the mechanism of methylation of G1405 by Sgm and compare it with other m7G methyltransferases, revealing a surprising diversity of active sites and binding modes for the same basic reaction of RNA modification. This analysis can serve as a stepping stone towards developing drugs that would specifically block the activity of Arm methyltransferases and thereby re-sensitize pathogenic bacteria to aminoglycoside antibiotics. 相似文献