全文获取类型
收费全文 | 1930篇 |
免费 | 149篇 |
出版年
2023年 | 7篇 |
2021年 | 27篇 |
2020年 | 17篇 |
2019年 | 23篇 |
2018年 | 40篇 |
2017年 | 27篇 |
2016年 | 63篇 |
2015年 | 82篇 |
2014年 | 99篇 |
2013年 | 114篇 |
2012年 | 154篇 |
2011年 | 128篇 |
2010年 | 85篇 |
2009年 | 81篇 |
2008年 | 119篇 |
2007年 | 118篇 |
2006年 | 126篇 |
2005年 | 98篇 |
2004年 | 98篇 |
2003年 | 109篇 |
2002年 | 88篇 |
2001年 | 10篇 |
2000年 | 16篇 |
1999年 | 23篇 |
1998年 | 24篇 |
1997年 | 24篇 |
1996年 | 18篇 |
1995年 | 13篇 |
1994年 | 16篇 |
1993年 | 10篇 |
1992年 | 9篇 |
1991年 | 10篇 |
1990年 | 12篇 |
1989年 | 5篇 |
1988年 | 12篇 |
1987年 | 9篇 |
1986年 | 10篇 |
1985年 | 11篇 |
1984年 | 12篇 |
1983年 | 12篇 |
1982年 | 14篇 |
1981年 | 14篇 |
1980年 | 15篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1976年 | 8篇 |
1975年 | 10篇 |
1974年 | 6篇 |
1973年 | 6篇 |
排序方式: 共有2079条查询结果,搜索用时 15 毫秒
71.
Intraguild predation by the generalist predator Orius majusculus on the parasitoid Encarsia formosa 总被引:1,自引:0,他引:1
Fariba Sohrabi Annie Enkegaard Parviz Shishehbor Moosa Saber Mohammad Said Mosaddegh 《BioControl》2013,58(1):65-72
Intraguild predation of Orius majusculus (Reuter) (Heteroptera: Anthocoridae) on Encarsia formosa (Gahan) (Hymenoptera: Aphelinidae), both natural enemies of Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae), was studied under laboratory conditions. The experiments quantified prey consumption by 5th instar nymphs and adults of O. majusculus offered unparasitised 3rd, early 4th or 4th instar B. tabaci nymphs or parasitised nymphs containing 2nd or 3rd larval instar or pupal parasitoids. In addition, prey preference of the two stages of O. majusculus for parasitised or unparasitised whitefly nymphs was studied using nine different prey combinations. Both predator stages readily preyed upon on both unparasitised and parasitised B. tabaci. In no-choice experiments, predation on 3rd instar E. formosa by adult predators was the highest, while predator nymphs preyed most on unparasitised 3rd instar B. tabaci and 2nd instar parasitoids. Predation of predator stages was lowest on 4th instar B. tabaci and E. formosa pupae. In all prey combinations, both stages of O. majusculus showed a significant preference for parasitised over unparasitised whitefly nymphs except for the combination of 5th instars of O. majusculus with early 4th instar whiteflies and E. formosa pupae. The results indicate that intraguild interactions between O. majusculus and E. formosa may have negative effects on biological control of B. tabaci. 相似文献
72.
73.
Vahan Kepenekian Marie-Thérèse Aloy Nicolas Magné Guillaume Passot Emma Armandy Evelyne Decullier Annie Sayag-Beaujard François-Noël Gilly Olivier Glehen Claire Rodriguez-Lafrasse 《Cell stress & chaperones》2013,18(5):623-630
Despite the strong rationale for combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis, thermotolerance and chemoresistance might result from heat shock protein overexpression. The aim of the present study was thus to determine whether the heat shock protein 27 (Hsp27), a potential factor in resistance to treatment, could have a higher level in serum from patients under this combined therapy. Patients receiving CRS plus HIPEC for peritoneal carcinomatosis (group 1), patients with cancer or a history of cancer undergoing abdominal surgery (group 2), and patients without malignancies undergoing abdominal surgery (group 3) were included. Hsp27 serum levels were determined before and at different times following CRS and HIPEC using enzyme-linked immunosorbent assay. In group 1 (n = 25), the high Hsp27 levels, observed at the end of surgery compared with before (p < 0.0001), decreased during HIPEC, but remained significantly higher than before surgery (p < 0.0005). In groups 2 (n = 11) and 3 (n = 15), surgery did not significantly increase Hsp27 levels. A targeted molecular strategy, inhibiting Hsp27 expression in tumor tissue, could significantly reduce resistance to the combined CRS plus HIPEC treatment. This approach should be further assessed in a clinical phase I trial. 相似文献
74.
Xavier Fioramonti Adam Deak Srinidhi Deshpande Lionel Carneiro Chunxue Zhou Nazish Sayed Branly Orban Joshua R. Berlin Luc Pénicaud Corinne Leloup Annie Beuve Vanessa H. Routh 《PloS one》2013,8(7)
Aims
Hypoglycemia is a severe side effect of intensive insulin therapy. Recurrent hypoglycemia (RH) impairs the counter-regulatory response (CRR) which restores euglycemia. During hypoglycemia, ventromedial hypothalamus (VMH) production of nitric oxide (NO) and activation of its receptor soluble guanylyl cyclase (sGC) are critical for the CRR. Hypoglycemia also increases brain reactive oxygen species (ROS) production. NO production in the presence of ROS causes protein S-nitrosylation. S-nitrosylation of sGC impairs its function and induces desensitization to NO. We hypothesized that during hypoglycemia, the interaction between NO and ROS increases VMH sGC S-nitrosylation levels and impairs the CRR to subsequent episodes of hypoglycemia. VMH ROS production and S-nitrosylation were quantified following three consecutive daily episodes of insulin-hypoglycemia (RH model). The CRR was evaluated in rats in response to acute insulin-induced hypoglycemia or via hypoglycemic-hyperinsulinemic clamps. Pretreatment with the anti-oxidant N-acetyl-cysteine (NAC) was used to prevent increased VMH S-nitrosylation.Results
Acute insulin-hypoglycemia increased VMH ROS levels by 49±6.3%. RH increased VMH sGC S-nitrosylation. Increasing VMH S-nitrosylation with intracerebroventricular injection of the nitrosylating agent S-nitroso-L-cysteine (CSNO) was associated with decreased glucagon secretion during hypoglycemic clamp. Finally, in RH rats pre-treated with NAC (0.5% in drinking water for 9 days) hypoglycemia-induced VMH ROS production was prevented and glucagon and epinephrine production was not blunted in response to subsequent insulin-hypoglycemia.Conclusion
These data suggest that NAC may be clinically useful in preventing impaired CRR in patients undergoing intensive-insulin therapy. 相似文献75.
Franck Desmoulin Michel Galinier Charlotte Trouillet Matthieu Berry Clément Delmas Annie Turkieh Pierre Massabuau Heinrich Taegtmeyer Fatima Smih Philippe Rouet 《PloS one》2013,8(4)
Objective
Mortality in heart failure (AHF) remains high, especially during the first days of hospitalization. New prognostic biomarkers may help to optimize treatment. The aim of the study was to determine metabolites that have a high prognostic value.Methods
We conducted a prospective study on a training cohort of AHF patients (n = 126) admitted in the cardiac intensive care unit and assessed survival at 30 days. Venous plasmas collected at admission were used for 1H NMR – based metabonomics analysis. Differences between plasma metabolite profiles allow determination of discriminating metabolites. A cohort of AHF patients was subsequently constituted (n = 74) to validate the findings.Results
Lactate and cholesterol were the major discriminating metabolites predicting 30-day mortality. Mortality was increased in patients with high lactate and low total cholesterol concentrations at admission. Accuracies of lactate, cholesterol concentration and lactate to cholesterol (Lact/Chol) ratio to predict 30-day mortality were evaluated using ROC analysis. The Lact/Chol ratio provided the best accuracy with an AUC of 0.82 (P < 0.0001). The acute physiology and chronic health evaluation (APACHE) II scoring system provided an AUC of 0.76 for predicting 30-day mortality. APACHE II score, Cardiogenic shock (CS) state and Lact/Chol ratio ≥ 0.4 (cutoff value with 82% sensitivity and 64% specificity) were significant independent predictors of 30-day mortality with hazard ratios (HR) of 1.11, 4.77 and 3.59, respectively. In CS patients, the HR of 30-day mortality risk for plasma Lact/Chol ratio ≥ 0.4 was 3.26 compared to a Lact/Chol ratio of < 0.4 (P = 0.018). The predictive power of the Lact/Chol ratio for 30-day mortality outcome was confirmed with the independent validation cohort.Conclusion
This study identifies the plasma Lact/Chol ratio as a useful objective and simple parameter to evaluate short term prognostic and could be integrated into quantitative guidance for decision making in heart failure care. 相似文献76.
Annie Albin Lumen Libin Li Jiben Li Zeba Ahmed Zhou Meng Albert Owen Harma Ellens Ismael J. Hidalgo Joe Bentz 《PloS one》2013,8(8)
We have reported that the P-gp substrate digoxin required basolateral and apical uptake transport in excess of that allowed by digoxin passive permeability (as measured in the presence of GF120918) to achieve the observed efflux kinetics across MDCK-MDR1-NKI (The Netherlands Cancer Institute) confluent cell monolayers. That is, GF120918 inhibitable uptake transport was kinetically required. Therefore, IC50 measurements using digoxin as a probe substrate in this cell line could be due to inhibition of P-gp, of digoxin uptake transport, or both. This kinetic analysis is now extended to include three additional cell lines: MDCK-MDR1-NIH (National Institute of Health), Caco-2 and CPT-B2 (Caco-2 cells with BCRP knockdown). These cells similarly exhibit GF120918 inhibitable uptake transport of digoxin. We demonstrate that inhibition of digoxin transport across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is greater than can be explained by inhibition of P-gp alone. We examined three hypotheses for this non-P-gp inhibition. The inhibitors can: (1) bind to a basolateral digoxin uptake transporter, thereby inhibiting digoxin''s cellular uptake; (2) partition into the basolateral membrane and directly reduce membrane permeability; (3) aggregate with digoxin in the donor chamber, thereby reducing the free concentration of digoxin, with concomitant reduction in digoxin uptake. Data and simulations show that hypothesis 1 was found to be uniformly acceptable. Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for GF120918 and cyclosporine, but further studies are needed to completely adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for ketoconazole and verapamil. We also find that P-gp substrates with relatively low passive permeability such as digoxin, loperamide and vinblastine kinetically require basolateral uptake transport over that allowed by +GF120918 passive permeability, while highly permeable P-gp substrates such as amprenavir, quinidine, ketoconazole and verapamil do not, regardless of whether they actually use the basolateral transporter. 相似文献
77.
Gilbert G. G. Donders Christophe E. Depuydt John-Paul Bogers Annie J. Vereecken 《PloS one》2013,8(12)
Objective
Is Trichomonas vaginalis (TV) an inducing factor for the development of (pre-)cancerous lesions of the cervix?Design
Cross sectional study.Setting
Screening healthy Belgian women with low infection risk.Sample
63,251 consecutive liquid based cervical samples.Methods
Real time quantitative PCR for presence of TV, 18 HPV types and Pap smear analysis of cytologic abnormalities.Main Outcome Measures
Association of TV and HPV with cervix dysplasiaResults
The overall prevalence of TV DNA was 0.37%, of low risk HPV 2%, of high risk HPV 13.2%, and 8.8 % had cytological abnormalities. Both LR-HPV and HR-HPV were significantly associated with all cytological abnormalities. Presence of TV was associated with LR- and HR-HPV, ASC-US and HSIL, but not with other abnormalities. All women with TV and HSIL also had HR-HPV, while the latter was present in only 59% of women with TV and ASC-US. Amongst HPV negative women, TV was found in 1.3% of women with ASC-US, but only in 0.03% of women with normal cytology (OR 4.2, CL95% 2.1-8.6). In HR-HPV positive women, presence of TV increased the likelihood of cytological abnormalities somewhat (P=0.05), mainly due to an increase in ASC-US and LSIL, but not HSIL.Conclusions
We conclude that TV infection is associated with both LR and HR-HPV infection of the cervix, as well as with ASC-US and HSIL. TV is a concomitant STI, but is not thought to be a co-factor in the causation of HSIL and cervical cancer. However, TV may cause false positive diagnoses of ASC-US. 相似文献78.
Anna Martinez Marie C. M. Halliez El Moukhtar Aliouat Magali Chabé Annie Standaert-Vitse Emilie Fréalle Nausicaa Gantois Muriel Pottier Anthony Pinon Eduardo Dei-Cas Cécile-Marie Aliouat-Denis 《PloS one》2013,8(11)
Pneumocystis organisms are airborne opportunistic pathogens that cannot be continuously grown in culture. Consequently, the follow-up of Pneumocystis stage-to-stage differentiation, the sequence of their multiplication processes as well as formal identification of the transmitted form have remained elusive. The successful high-speed cell sorting of trophic and cystic forms is paving the way for the elucidation of the complex Pneumocystis life cycle. The growth of each sorted Pneumocystis stage population was followed up independently both in nude rats and in vitro. In addition, by setting up a novel nude rat model, we attempted to delineate which cystic and/or trophic forms can be naturally aerially transmitted from host to host. The results showed that in axenic culture, cystic forms can differentiate into trophic forms, whereas trophic forms are unable to evolve into cystic forms. In contrast, nude rats inoculated with pure trophic forms are able to produce cystic forms and vice versa. Transmission experiments indicated that 12 h of contact between seeder and recipient nude rats was sufficient for cystic forms to be aerially transmitted. In conclusion, trophic- to cystic-form transition is a key step in the proliferation of Pneumocystis microfungi because the cystic forms (but not the trophic forms) can be transmitted by aerial route from host to host. 相似文献
79.
Aims
Acute ethanol intoxication (AEI) attenuates the arginine vasopressin (AVP) response to hemorrhage leading to impaired hemodynamic counter-regulation and accentuated hemodynamic stability. Previously we identified that the ethanol-induced impairment of circulating AVP concentrations in response to hemorrhage was the result of augmented central nitric oxide (NO) inhibition. The aim of the current study was to examine the mechanisms underlying ethanol-induced up-regulation of paraventricular nucleus (PVN) NO concentration. Angiotensin (ANG) (1-7) is an important mediator of NO production through activation of the Mas receptor. We hypothesized that Mas receptor inhibition would decrease central NO concentration and thus restore the rise in circulating AVP levels during hemorrhagic shock in AEI rats.Main methods
Conscious male Sprague–Dawley rats (300–325 g) received a 15 h intra-gastric infusion of ethanol (2.5 g/kg + 300 mg/kg/h) or dextrose prior to a fixed-pressure (~ 40 mm Hg) 60 min hemorrhage. The Mas receptor antagonist A-779 was injected through an intracerebroventricular (ICV) cannula 15 min prior to hemorrhage.Key findings
PVN NOS activity and NO were significantly higher in AEI compared to DEX-treated controls at the completion of hemorrhage. ICV A-779 administration decreased NOS activity and NO concentration, partially restoring the rise in circulating AVP level at completion of hemorrhage in AEI rats.Significance
These results suggest that Mas receptor activation contributes to the NO-mediated inhibitory tone of AVP release in the ethanol-intoxicated hemorrhaged host. 相似文献80.
Annie Bouchard-Mercier Iwona Rudkowska Simone Lemieux Patrick Couture Marie-Claude Vohl 《Journal of lipid research》2013,54(10):2866-2873
Interindividual variability in the response of plasma triglyceride concentrations (TG) following fish oil consumption has been observed. Our objective was to examine the associations between single-nucleotide polymorphisms (SNPs) within genes encoding proteins involved in de novo lipogenesis and the relative change in plasma TG levels following a fish oil supplementation. Two hundred and eight participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9–2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid. SNPs within SREBF1, ACLY, and ACACA genes were genotyped using TAQMAN methodology. After correction for multiple comparison, only two SNPs, rs8071753 (ACLY) and rs1714987 (ACACA), were associated with the relative change in plasma TG concentrations (P = 0.004 and P = 0.005, respectively). These two SNPs explained 7.73% of the variance in plasma TG relative change following fish oil consumption. Genotype frequencies of rs8071753 according to the TG response groups (responders versus nonresponders) were different (P = 0.02). We conclude that the presence of certain SNPs within genes, such as ACLY and ACACA, encoding proteins involved in de novo lipogenesis seem to influence the plasma TG response following fish oil consumption. 相似文献