全文获取类型
收费全文 | 42481篇 |
免费 | 3095篇 |
国内免费 | 7篇 |
专业分类
45583篇 |
出版年
2023年 | 326篇 |
2022年 | 509篇 |
2021年 | 995篇 |
2020年 | 768篇 |
2019年 | 985篇 |
2018年 | 1284篇 |
2017年 | 1192篇 |
2016年 | 1674篇 |
2015年 | 2097篇 |
2014年 | 2226篇 |
2013年 | 3005篇 |
2012年 | 3501篇 |
2011年 | 3315篇 |
2010年 | 2142篇 |
2009年 | 1843篇 |
2008年 | 2409篇 |
2007年 | 2289篇 |
2006年 | 2161篇 |
2005年 | 1783篇 |
2004年 | 1734篇 |
2003年 | 1585篇 |
2002年 | 1399篇 |
2001年 | 676篇 |
2000年 | 629篇 |
1999年 | 526篇 |
1998年 | 401篇 |
1997年 | 278篇 |
1996年 | 273篇 |
1995年 | 270篇 |
1994年 | 197篇 |
1993年 | 193篇 |
1992年 | 273篇 |
1991年 | 218篇 |
1990年 | 183篇 |
1989年 | 181篇 |
1988年 | 159篇 |
1987年 | 164篇 |
1986年 | 147篇 |
1985年 | 128篇 |
1984年 | 167篇 |
1983年 | 115篇 |
1982年 | 120篇 |
1981年 | 107篇 |
1980年 | 85篇 |
1979年 | 90篇 |
1978年 | 73篇 |
1976年 | 53篇 |
1975年 | 55篇 |
1974年 | 80篇 |
1973年 | 64篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
Synthesis and antifungal activity of diverse C-2 pyridinyl and pyridinylvinyl substituted quinolines
Vladimir V. Kouznetsov Carlos M. Meléndez Gómez Marcos G. Derita Laura Svetaz Esther del Olmo Susana A. Zacchino 《Bioorganic & medicinal chemistry》2012,20(21):6506-6512
Diverse 2-pyridinyl quinolines 6–12 and 2-pyridinilvinyl quinolines 13–17 were prepared using a straightforward synthesis based on the BiCl3-catalyzed multicomponent imino Diels–Alder (imino DA) reaction or a novel tandem imino DA/catalytic tetrahydroquinoline ring oxidation/Perkin condensation sequential process. All members of the series showed activities against dermatophytes and some of them possessed a broad spectrum of action. 2-(Pyridin-4-yl)quinoline 9 and 2-(2-pyridin-4-yl)vinyl)quinoline 16 showed the best MIC80 and MIC50 against the clinically important fungi Candida albicans and non-albicans Candida species. In turn, 6-ethyl-2-(pyridin-2-yl)quinoline 6 showed the best properties against standardized as well as clinical strains of Cryptococcus neoformans. 相似文献
992.
BackgroundInvasive fungal infection (IFI) is an entity that encompasses different types of infections caused by different types of those fungi pathogenic for humans. In the setting of critically ill patients with multiple and oftenconcurrent risk factors and comorbidities the most common are those caused by the Candida and Aspergillus species. Among the characteristics of IFI in critically ill patients, three aspects can be highlighted: those related to the host (e.g.: risk factors, clinical severity), those related with the pathogen (sensitivity, virulence), or those concerning antifungal treatment (spectrum, features PK / PD, safety, interactions). The fungus that most often causes an IFI in critically ill patients is Candida; the most common type infections are candidemia, Candida peritonitis and catheter-related infections. In recent years new antifungal treatments have expanded the therapeutic options, with echinocandins as a clear choice, often the first in the latest guidelines in critically ill patients with IFI.Case reportWe report the case of a critically ill patient having the most common risk factors, multiple organ dysfunction and development of an IFI. The complexity of establishing an antifungal treatment from the moment of its inception, its setting, and the considerations of the different therapeutic possibilities according to organ dysfunction of the patient are discussed. The antifungal treatment options mentioned in the current guidelines and recommendations are also evaluated.ConclusionsThe most common fungal infection in critically ill patients is invasive candidiasis, with candidemia or candida peritonitis being the most frequent clinical presentations. Candins have brought new possibilities for treating these complex patients due to their good safety profile and clinical efficacy. 相似文献
993.
The Amazon harbours one of the richest ecosystems on Earth. Such diversity is likely to be promoted by plant specialization, associated with the occurrence of a mosaic of landscape units. Here, we integrate ecological and phylogenetic data at different spatial scales to assess the importance of habitat specialization in driving compositional and phylogenetic variation across the Amazonian forest. To do so, we evaluated patterns of floristic dissimilarity and phylogenetic turnover, habitat association and phylogenetic structure in three different landscape units occurring in terra firme (Hilly and Terrace) and flooded forests (Igapó). We established two 1-ha tree plots in each of these landscape units at the Caparú Biological Station, SW Colombia, and measured edaphic, topographic and light variables. At large spatial scales, terra firme forests exhibited higher levels of species diversity and phylodiversity than flooded forests. These two types of forests showed conspicuous differences in species and phylogenetic composition, suggesting that environmental sorting due to flood is important, and can go beyond the species level. At a local level, landscape units showed floristic divergence, driven both by geographical distance and by edaphic specialization. In terms of phylogenetic structure, Igapó forests showed phylogenetic clustering, whereas Hilly and Terrace forests showed phylogenetic evenness. Within plots, however, local communities did not show any particular trend. Overall, our findings suggest that flooded forests, characterized by stressful environments, impose limits to species occurrence, whereas terra firme forests, more environmentally heterogeneous, are likely to provide a wider range of ecological conditions and therefore to bear higher diversity. Thus, Amazonia should be considered as a mosaic of landscape units, where the strength of habitat association depends upon their environmental properties. 相似文献
994.
Alberto Bouzas-Mosquera Francisco J. Broullón Nemesio álvarez-García Jesús Peteiro Víctor X. Mosquera Alfonso Castro-Beiras 《PloS one》2012,7(9)
Background
Our aim was to assess the association of left ventricular mass with mortality and nonfatal cardiovascular events.Methodology/Principal Findings
Left ventricular mass was measured by echocardiography in 40138 adult patients (mean age 61.1±16.4 years, 52.5% male). The primary endpoint was all-cause mortality. Secondary endpoints included nonfatal myocardial infarction and nonfatal stroke. During a mean follow-up period of 5.6±3.9 years, 9181 patients died, 901 patients had a nonfatal myocardial infarction, and 2139 patients had a nonfatal stroke. Cumulative 10-year mortality was 26.8%, 31.9%, 37.4% and 46.4% in patients with normal, mildly, moderately and severely increased left ventricular mass, respectively (p<0.001). Ten-year rates of nonfatal myocardial infarction and stroke ranged from 3.2% and 6.7% in patients with normal left ventricular mass to 5.3% and 12.7% in those with severe increase in left ventricular mass, respectively. After multivariate adjustment, left ventricular mass remained an independent predictor of all-cause mortality (hazard ratio [HR] per 100 g increase 1.21, 95% confidence interval [CI] 1.14–1–27, p<0.001 in women, and HR 1.09, 95% CI 1.04–1–13, p<0.001 in men), myocardial infarction (HR 1.60, 95% CI 1.31–1.94, p<0.001 in women and HR 1.15, 95% CI 1.02–1.29, p = 0.019 in men) and stroke (HR 1.26, 95% CI 1.13–1.40, p<0.001 in women and HR 1.19, 95% CI 1.09–1.30, p<0.001 in men).Conclusions/Significance
Left ventricular mass has a graded and independent association with all-cause mortality, myocardial infarction and stroke. 相似文献995.
996.
A. Pons F.J. García A. Palou A. Alemany 《Journal of biochemical and biophysical methods》1981,5(3):153-156
A method for quantitative estimation of total radioactivity present in the free amino acid fraction of tissue samples has been described. Samples deproteinized with cold acetone were extracted, in acidic medium, with ethyl (peroxide free); after centrifugation, the aqueous phase was used for amino acid derivatization at 40°C for 15 h with 1-flouro-2,4-dinitrobenzene in bicarbonate-buffered medium. Aliquots of the derivatized samples were acidified and extracted twice again with ethyl ether. The combined organic phases were placed in glass scintilation vials, dried, and used for the determination of its radiactivity, corresponding to the radioactivity present in the free amino acid fraction of the sample. Deproteinized samples of rat blood plasma, as well as hen egg white and yolk were tested after addition of known quantities of 14C-labelled amino acids or glucose, for validation of the method. No glucose radioactivity was found in any of the extracted samples. All radioactivity added to the samples in the form of 14C-labelled alanine, glutamic acid, leucine and phenylalanine was quantitatively recovered in the derivatized fraction; only a fraction of arginine radioactivity was recovered. 相似文献
997.
In the present work the effects of the hypophysis hormones on oviduct mucoprotein components distribution patterns were studied. Remarkable changes after treating the toad with hypophysis injections were apparent. The distribution pattern for hexose, sialic acid, hexosamine and phosphate from 18 hours hypophysis treated toads were found to be identical with those obtained from preovulatory period animals. On the other hand, the levels for mucoprotein components from hypophysis treated animals were found to be approximately one-half or more higher than those obtained from postovulatory period toads. Otherwise, hypophysis treatment of the toads in preovulatory period had not effect on the levels and distribution patterns of mucoprotein components. These results suggest that hypophysis hormones are involved in the increase of the oviduct secretory activity. 相似文献
998.
999.
Purification and characterization of an extracellular protease from Penicillium chrysogenum Pg222 active against meat proteins 总被引:1,自引:0,他引:1
Benito MJ Rodríguez M Núñez F Asensio MA Bermúdez ME Córdoba JJ 《Applied and environmental microbiology》2002,68(7):3532-3536
An extracellular protease from Penicillium chrysogenum (Pg222) isolated from dry-cured ham has been purified. The purification procedure involved several steps: ammonium sulfate precipitation, ion-exchange chromatography, filtration, and separation by high-performance liquid chromatography. Based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis and gel filtration, the purified fraction showed a molecular mass of about 35 kDa. The hydrolytic properties of the purified enzyme (EPg222) on extracted pork myofibrillar proteins under several conditions were evaluated by SDS-PAGE. EPg222 showed activity in the range of 10 to 60 degrees C in temperature, 0 to 3 M NaCl, and pH 5 to 7, with maximum activity at pH 6, 45 degrees C, and 0.25 M NaCl. Under these conditions the enzyme was most active against tropomyosin, actin, and myosin. EPg222 showed collagenolytic activity but did not hydrolyze myoglobin. EPg222 showed higher activity than other proteolytic enzymes like papain, trypsin, and Aspergillus oryzae protease. The N-terminal amino acid sequence was determined and was found to be Glu-Asn-Pro-Leu-Gln-Pro-Asn-Ala-Pro-Ser-Trp. This partial amino acid sequence revealed a 55% homology with serine proteases from Penicillium citrinum. The activity of this novel protease may be of interest in ripening and generating the flavor of dry-cured meat products. 相似文献
1000.
Lou L Urbani J Ribeiro-Neto F Altschuler DL 《The Journal of biological chemistry》2002,277(36):32799-32806
Rap1b has been implicated in the transduction of the cAMP mitogenic signal. Rap1b is phosphorylated and activated by cAMP, and its expression in cells where cAMP is mitogenic leads to an increase in G(1)/S phase entry and tumor formation. The PCCL3 thyroid follicular cells represent a differentiated and physiologically relevant system that requires thyrotropin (TSH), acting via cAMP, for a full mitogenic response. In this model system, cAMP stimulation of DNA synthesis requires activation and phosphorylation of Rap1b by the cAMP-dependent protein kinase A (PKA). This scenario presents the challenge of identifying biochemical processes involved in the phosphorylation-dependent Rap1b mitogenic action. In thyroid cells, Akt has been implicated in the stimulation of cell proliferation by TSH and cAMP. However, the mechanism(s) by which cAMP regulates Akt activity remains unclear. In this study we show that in PCCL3 cells 1) TSH inhibits Akt activity via cAMP and PKA; 2) Rap1b is required for cAMP inhibition of Akt; and 3) transduction of the cAMP signal into Akt requires activation as well as phosphorylation of Rap1b by PKA. 相似文献