全文获取类型
收费全文 | 6299篇 |
免费 | 485篇 |
国内免费 | 2篇 |
出版年
2023年 | 31篇 |
2022年 | 92篇 |
2021年 | 157篇 |
2020年 | 106篇 |
2019年 | 126篇 |
2018年 | 160篇 |
2017年 | 140篇 |
2016年 | 224篇 |
2015年 | 329篇 |
2014年 | 328篇 |
2013年 | 555篇 |
2012年 | 562篇 |
2011年 | 498篇 |
2010年 | 332篇 |
2009年 | 254篇 |
2008年 | 400篇 |
2007年 | 395篇 |
2006年 | 362篇 |
2005年 | 267篇 |
2004年 | 276篇 |
2003年 | 262篇 |
2002年 | 236篇 |
2001年 | 48篇 |
2000年 | 34篇 |
1999年 | 55篇 |
1998年 | 57篇 |
1997年 | 51篇 |
1996年 | 45篇 |
1995年 | 30篇 |
1994年 | 40篇 |
1993年 | 42篇 |
1992年 | 27篇 |
1991年 | 21篇 |
1990年 | 22篇 |
1989年 | 13篇 |
1988年 | 14篇 |
1987年 | 16篇 |
1986年 | 12篇 |
1985年 | 10篇 |
1984年 | 18篇 |
1983年 | 15篇 |
1982年 | 18篇 |
1981年 | 17篇 |
1980年 | 7篇 |
1978年 | 13篇 |
1977年 | 8篇 |
1976年 | 6篇 |
1974年 | 7篇 |
1973年 | 7篇 |
1972年 | 6篇 |
排序方式: 共有6786条查询结果,搜索用时 15 毫秒
191.
192.
193.
Gianluigi Savarese Bruno Trimarco Santo Dellegrottaglie Maria Prastaro Francesco Gambardella Giuseppe Rengo Dario Leosco Pasquale Perrone-Filardi 《PloS one》2013,8(3)
Background
The role of cardiac natriuretic peptides in the management of patients with chronic heart failure (HF) remains uncertain. The purpose of this study was to evaluate whether natriuretic peptide-guided therapy, compared to clinically-guided therapy, improves mortality and hospitalization rate in patients with chronic HF.Methodology/Principal Findings
MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched for articles reporting natriuretic peptide-guided therapy in HF until August 2012. All randomized trials reporting clinical end-points (all-cause mortality and/or HF-related hospitalization and/or all-cause hospitalization) were included. Meta-analysis was performed to assess the influence of treatment on outcomes. Sensitivity analysis was performed to test the influence of potential effect modifiers and of each trial included in meta-analysis on results. Twelve trials enrolling 2,686 participants were included. Natriuretic peptide-guided therapy (either B-type natriuretic peptide [BNP]- or N-terminal pro-B-type natriuretic peptide [NT-proBNP]-guided therapy) significantly reduced all-cause mortality (Odds Ratio [OR]:0.738; 95% Confidence Interval [CI]:0.596 to 0.913; p = 0.005) and HF-related hospitalization (OR:0.554; CI:0.399 to 0.769; p = 0.000), but not all-cause hospitalization (OR:0.803; CI:0.629 to 1.024; p = 0.077). When separately assessed, NT-proBNP-guided therapy significantly reduced all-cause mortality (OR:0.717; CI:0.563 to 0.914; p = 0.007) and HF-related hospitalization (OR:0.531; CI:0.347 to 0.811; p = 0.003), but not all-cause hospitalization (OR:0.779; CI:0.414 to 1.465; p = 0.438), whereas BNP-guided therapy did not significantly reduce all-cause mortality (OR:0.814; CI:0.518 to 1.279; p = 0.371), HF-related hospitalization (OR:0.599; CI:0.303 to 1.187; p = 0.142) or all-cause hospitalization (OR:0.726; CI:0.609 to 0.964; p = 0.077).Conclusions/Significance
Use of cardiac peptides to guide pharmacologic therapy significantly reduces mortality and HF related hospitalization in patients with chronic HF. In particular, NT-proBNP-guided therapy reduced all-cause mortality and HF-related hospitalization but not all-cause hospitalization, whereas BNP-guided therapy did not significantly reduce both mortality and morbidity. 相似文献194.
Tick-borne zoonoses are considered as emerging diseases. Tick repellents represent an effective tool for reducing the risk of tick bite and pathogens transmission. Previous work demonstrated the repellent activity of the phenylpropanoid eugenol against Ixodes ricinus; here we investigate the relationship between molecular structure and repellency in a group of substances related to that compound. We report the biological activity of 18 compounds varying for the presence/number of several moieties, including hydroxyl and methoxy groups and carbon side-chain. Each compound was tested at different doses with a bioassay designed to measure repellency against individual tick nymphs. Both vapor pressure and chemical features of the tested compounds appeared to be related to repellency. In particular, the hydroxyl and methoxy groups as well as the side-chain on the benzene ring seem to play a role. These results are discussed in light of available data on chemical perception in ticks. In the course of the study new repellent compounds were identified; the biological activity of some of them (at least as effective as the “gold standard” repellent DEET) appears to be very promising from a practical point of view. 相似文献
195.
Francesco Addabbo Qiuying Chen Dhara P. Patel May Rabadi Brian Ratliff Frank Zhang Jean-Francois Jasmin Michael Wolin Michael Lisanti Steven S. Gross Michael S. Goligorsky 《PloS one》2013,8(6)
Endothelial Cell Dysfunction (ECD) is a recognized harbinger of a host of chronic cardiovascular diseases. Using a mouse model of ECD triggered by treatment with L-Nω-methylarginine (L-NMMA), we previously demonstrated that renal microvasculature displays a perturbed protein profile, including diminished expression of two key enzymes of the Krebs cycle associated with a Warburg-type suppression of mitochondrial metabolism. We hypothesized that supplementation with L-glutamine (GLN), that can enter the Krebs cycle downstream this enzymatic bottleneck, would normalize vascular function and alleviate mitochondrial dysfunction. To test this hypothesis, mice with chronic L-NMMA-induced ECD were co-treated with GLN at different concentrations for 2 months. Results confirmed that L-NMMA led to a defect in acetylcholine-induced relaxation of aortic rings that was dose-dependently prevented by GLN. In caveolin-1 transgenic mice characterized by eNOS inactivation, L-NMMA further impaired vasorelaxation which was partially rescued by GLN co-treatment. Pro-inflammatory profile induced by L-NMMA was blunted in mice co-treated with GLN. Using an LC/MS platform for metabolite profiling, we sought to identify metabolic perturbations associated with ECD and offset by GLN supplementation. 3453 plasma molecules could be detected with 100% frequency in mice from at least one treatment group. Among these, 37 were found to be differentially expressed in a 4-way comparison of control vs. LNMMA both with and without GLN. One of such molecules, hippuric acid, an “uremic toxin” was found to be elevated in our non-uremic mice receiving L-NMMA, but normalized by treatment with GLN. Ex vivo analysis of hippuric acid effects on vasomotion demonstrated that it significantly reduced acetylcholine-induced vasorelaxation of vascular rings. In conclusion, functional and metabolic profiling of animals with early ECD revealed macrovasculopathy and that supplementation GLN is capable of improving vascular function. Metabolomic analyses reveal elevation of hippuric acid, which may further exacerbate vasculopathy even before the development of uremia. 相似文献
196.
197.
198.
Vincenzo Verdoliva Cinzia Senatore Maria Letizia Polci Stefania Rossi Martina Cordella Giuseppe Carlucci Paolo Marchetti Giancarlo Antonini-Cappellini Antonio Facchiano Daniela D'Arcangelo Francesco Facchiano 《PloS one》2013,8(3)
Recently developed proteomic technologies allow to profile thousands of proteins within a high-throughput approach towards biomarker discovery, although results are not as satisfactory as expected. In the present study we demonstrate that serum proteome denaturation is a key underestimated feature; in fact, a new differential denaturation protocol better discriminates serum proteins according to their electrophoretic mobility as compared to single-denaturation protocols. Sixty nine different denaturation treatments were tested and the 3 most discriminating ones were selected (TRIDENT analysis) and applied to human sera, showing a significant improvement of serum protein discrimination as confirmed by MALDI-TOF/MS and LC-MS/MS identification, depending on the type of denaturation applied. Thereafter sera from mice and patients carrying cutaneous melanoma were analyzed through TRIDENT. Nine and 8 protein bands were found differentially expressed in mice and human melanoma sera, compared to healthy controls (p<0.05); three of them were found, for the first time, significantly modulated: α2macroglobulin (down-regulated in melanoma, p<0.001), Apolipoprotein-E and Apolipoprotein-A1 (both up-regulated in melanoma, p<0.04), both in mice and humans. The modulation was confirmed by immunological methods. Other less abundant proteins (e.g. gelsolin) were found significantly modulated (p<0.05).Conclusions: i) serum proteome contains a large amount of information, still neglected, related to proteins folding; ii) a careful serum denaturation may significantly improve analytical procedures involving complex protein mixtures; iii) serum differential denaturation protocol highlights interesting proteomic differences between cancer and healthy sera. 相似文献
199.
Jan Mládek Pavla Mládková Pavla Hejcmanová Miroslav Dvorsky Vilém Pavlu Francesco De Bello Martin Duchoslav Michal Hejcman Robin J. Pakeman 《PloS one》2013,8(7)
Background
Current plant – herbivore interaction models and experiments with mammalian herbivores grazing plant monocultures show the superiority of a maximizing forage quality strategy (MFQ) over a maximizing intake strategy (MI). However, there is a lack of evidence whether grazers comply with the model predictions under field conditions.Methodology/Findings
We assessed diet selection of sheep (Ovis aries) using plant functional traits in productive mesic vs. low-productivity dry species-rich grasslands dominated by resource-exploitative vs. resource-conservative species respectively. Each grassland type was studied in two replicates for two years. We investigated the first grazing cycle in a set of 288 plots with a diameter of 30 cm, i.e. the size of sheep feeding station. In mesic grasslands, high plot defoliation was associated with community weighted means of leaf traits referring to high forage quality, i.e. low leaf dry matter content (LDMC) and high specific leaf area (SLA), with a high proportion of legumes and the most with high community weighted mean of forage indicator value. In contrast in dry grasslands, high community weighted mean of canopy height, an estimate of forage quantity, was the best predictor of plot defoliation. Similar differences in selection on forage quality vs. quantity were detected within plots. Sheep selected plants with higher forage indicator values than the plot specific community weighted mean of forage indicator value in mesic grasslands whereas taller plants were selected in dry grasslands. However, at this scale sheep avoided legumes and plants with higher SLA, preferred plants with higher LDMC while grazing plants with higher forage indicator values in mesic grasslands.Conclusions
Our findings indicate that MFQ appears superior over MI only in habitats with a predominance of resource-exploitative species. Furthermore, plant functional traits (LDMC, SLA, nitrogen fixer) seem to be helpful correlates of forage quality only at the community level. 相似文献200.
Ray-finned fishes constitute the dominant radiation of vertebrates with over 32,000 species. Although molecular phylogenetics has begun to disentangle major evolutionary relationships within this vast section of the Tree of Life, there is no widely available approach for efficiently collecting phylogenomic data within fishes, leaving much of the enormous potential of massively parallel sequencing technologies for resolving major radiations in ray-finned fishes unrealized. Here, we provide a genomic perspective on longstanding questions regarding the diversification of major groups of ray-finned fishes through targeted enrichment of ultraconserved nuclear DNA elements (UCEs) and their flanking sequence. Our workflow efficiently and economically generates data sets that are orders of magnitude larger than those produced by traditional approaches and is well-suited to working with museum specimens. Analysis of the UCE data set recovers a well-supported phylogeny at both shallow and deep time-scales that supports a monophyletic relationship between Amia and Lepisosteus (Holostei) and reveals elopomorphs and then osteoglossomorphs to be the earliest diverging teleost lineages. Our approach additionally reveals that sequence capture of UCE regions and their flanking sequence offers enormous potential for resolving phylogenetic relationships within ray-finned fishes. 相似文献