全文获取类型
收费全文 | 3801篇 |
免费 | 254篇 |
国内免费 | 2篇 |
出版年
2023年 | 25篇 |
2022年 | 50篇 |
2021年 | 101篇 |
2020年 | 60篇 |
2019年 | 92篇 |
2018年 | 94篇 |
2017年 | 91篇 |
2016年 | 142篇 |
2015年 | 208篇 |
2014年 | 224篇 |
2013年 | 271篇 |
2012年 | 343篇 |
2011年 | 298篇 |
2010年 | 185篇 |
2009年 | 176篇 |
2008年 | 212篇 |
2007年 | 213篇 |
2006年 | 223篇 |
2005年 | 170篇 |
2004年 | 167篇 |
2003年 | 155篇 |
2002年 | 137篇 |
2001年 | 31篇 |
2000年 | 31篇 |
1999年 | 41篇 |
1998年 | 31篇 |
1997年 | 26篇 |
1996年 | 18篇 |
1995年 | 22篇 |
1994年 | 16篇 |
1993年 | 23篇 |
1992年 | 20篇 |
1991年 | 17篇 |
1990年 | 11篇 |
1989年 | 7篇 |
1988年 | 11篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 10篇 |
1983年 | 5篇 |
1982年 | 12篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1978年 | 12篇 |
1977年 | 5篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1973年 | 4篇 |
排序方式: 共有4057条查询结果,搜索用时 15 毫秒
101.
Julio C. López-Doval Antoni Ginebreda Thierry Caquet Clifford N. Dahm Mira Petrovic Damià Barceló Isabel Muñoz 《Hydrobiologia》2013,719(1):427-450
This review examines information generated over the past decade on the pollution of rivers in regions with a mediterranean-type climate (med-climate). Pollution has clearly increased in the last 100 years and is correlated with the development of industry, agriculture and human population. Important efforts have been made in some med-climate countries in order to characterise the chemical status of rivers. In addition, the number of chemical substances detectable in mediterranean-climate rivers (med-rivers), as well as the limits of detection, have improved from the development of better analytical methods. New substances detected in rivers are gaining attention. We discuss available knowledge regarding real and potential effects of pollutants on the biota and ecosystems in med-rivers, taking into account natural environmental characteristics of these rivers. The extreme seasonal conditions in med-rivers add to the potential risk because these characteristics can enhance pollutant effects. Efforts and policies to prevent or reduce pollution effects on med-rivers are linked to the knowledge about pollution pressures associated with the degree of economic development. Aquatic communities in med-rivers are more sensitive to pollutants because they are exposed to strong natural and human stressors. 相似文献
102.
Maria Rosa Buemi Laura De Luca Alba Chimirri Stefania Ferro Rosaria Gitto Julio Alvarez-Builla Ramon Alajarin 《Bioorganic & medicinal chemistry》2013,21(15):4575-4580
Several indole derivatives, that were highly potent ligands of GluN2B-subunit-containing N-methyl-d-aspartate (NMDA) receptor, also demonstrated antioxidant properties in ABTS method. In particular, the 2-(4-benzylpiperidin-1-yl)-1-(5-hydroxy-1H-indol-3-yl)ethanone (1) proved to be a dual-effective neuroprotective agent. With the aim to increase the antioxidant properties we added a catechol moiety onto piperidine moiety. The designed hybrid derivative 3,4-dihydroxy-N-[1-[2-(5-hydroxy-1H-indol-3-yl)-2-oxoethyl]piperidin-4-yl]benzamide (10) was the most effective antioxidant agent (>94.1 ± 0.1% of inhibition at 17 μM) and showed GluN2B/NMDA receptor affinity at low micromolar concentration (IC50 0.66 μM). By means of computational studies we explored the effect of the presence of this antioxidant fragment during the recognition process to binding pocket. 相似文献
103.
Ana I. Sánchez Valentín Martínez-Barrasa Carolina Burgos Juan J. Vaquero Julio Alvarez-Builla Emma Terricabras Víctor Segarra 《Bioorganic & medicinal chemistry》2013,21(8):2370-2378
The latest scientific findings concerning PDE7 and PDE4 inhibition suggest that selective small-molecule inhibitors of both enzymes could provide a novel approach to treat a variety of immunological diseases. In this context, we describe a new series of quinazoline derivatives from quinazolin-4-thiones which include a substituted biphenyl fragment. Some of these compounds show inhibitory potencies at sub-micromolar levels against the catalytic domain of PDE7. 相似文献
104.
Lucas C. Pantaleão Gabriela F.R. Teodoro Francisco L. Torres-Leal Daiana Vianna Tatyana D. de Paula Emídio M. de Matos-Neto Michele C.C. Trindade Marcelo M. Rogero Carlos R. Bueno Julio Tirapegui 《The Journal of nutritional biochemistry》2013,24(7):1340-1348
The positive regulation of insulin pathway in skeletal muscle results in increased activity of the mammalian target of rapamycin (mTOR), a positive effector of mRNA translation rate and protein synthesis. Studies that assess the activity of this protein in response to chronic high-fat diet (HFD) are scarce and controversial, and to date, there are no studies evaluating the mTOR pathway in infants exposed to gestational and postgestational HFD. This study investigated the effect of maternal HFD on skeletal muscle morphology and on phosphorylation of proteins that comprise the intracellular mTOR signaling pathway in soleus muscle of offspring at weaning. For this purpose, 10 days prior to conception, 39 female Wistar rats were randomly assigned to either control diet (CTL) or HFD. Later, rats were distributed into four groups according to gestational and postpregnancy diet: CTL/CTL (n=10), CTL/HF (n=11), HF/HF (n=10) and HF/CTL (n=8). After 21 days of lactation, pups were killed, and blood samples and soleus and gastrocnemius skeletal muscle were collected for analysis. We observed an influence of maternal postgestational diet, rather than gestational diet, in promoting an obese phenotype, characterized by body fat accumulation, insulin resistance and high serum leptin, glucose, triglycerides and cholesterol levels (P<.05). We have also detected alterations on skeletal muscle morphology — with reduced myofiber density — and impairment on S6 kinase 1 and 4E binding protein-1 phosphorylation (P<.05). These results emphasize the importance of maternal diet during lactation on muscle morphology and on physiological adaptations of infant rats. 相似文献
105.
106.
Cristine Rodrigues Luciana P. S. Vandenberghe Wilerson Sturm Dario E. A. Dergint Michele Rigon Spier Júlio Cesar de Carvalho Carlos R. Soccol 《World journal of microbiology & biotechnology》2013,29(12):2317-2324
Citric acid (CA) is one of the most important products of fermentation in the world. A great variety of agro-industrial residues can be used in solid state fermentation. Aspergillus niger parental strain (CCT 7716) and two strains obtained by mutagenesis (CCT 7717 and CCT 7718) were evaluated in Erlenmeyer flasks and glass columns using citric pulp (CP) as substrate/support, sugarcane molasses and methanol. Best results using glass columns (forced aeration) were found in the fourth day of fermentation: 278.4, 294.9 and 261.1 g CA/kg of dry CP with CCT 7716, CCT 7718 and CCT 7717, respectively. In Erlenmeyer flasks (aeration by diffusion) CA reached 410.7, 446.8 and 492.7 g CA/kg of dry CP with CCT 7716, CCT 7718 and CCT 7717, respectively. The aeration by diffusion improved CA production by the three strains. A data acquisition system specially developed for biotechnological processes analysis was used to perform the respirometric parameters measurement. 相似文献
107.
Vanessa Bueno Paulo Cesar Venere Claudio Henrique Zawadzki Vladimir Pavan Margarido 《Reviews in Fish Biology and Fisheries》2013,23(1):103-112
Hypostomus is a species-rich genus of fish with unclear systematics and phylogenetic relationships. Ten species of Hypostomus (H. albopunctatus, H. ancistroides, H. cochliodon, H. commersoni, H. faveolus, H. hermanni, H. aff. paulinus, H. regani, H. strigaticeps and H. topavae) were cytogenetically analyzed through Giemsa staining and silver nitrate impregnation, and the obtained data were correlated to the available biogeographical and phylogenetic analyses for the genus. Although the silver stained nucleolar organizer regions (AgNORs) were found to vary significantly among the species, the diploid numbers could be correlated to the distribution of the species on northern and southern South America river basins. Species with the lower diploid numbers (2n = 64) were associated to northern hydrographic basins and showed a single AgNORs bearing pair. Diploid numbers of 66–68 chromosomes and of 70–84 chromosomes were correlated to two major clades within Hypostomus and southern hydrographic basins, and showed AgNORs varying on number and position. Our results show that cytogenetic data can be correlated to the phylogeny and biogeography of the genus, helping to clarify its complex evolutionary history. 相似文献
108.
Aneta Radziwon-Balicka Cesar Moncada de la Rosa Barbara Zielnik Adrian Doroszko Paul Jurasz 《PloS one》2013,8(3)
Platelets play an important role in thrombosis and in neo-vascularisation as they release and produce factors that both promote and suppress angiogenesis. Amongst these factors is the angiogenesis inhibitor angiostatin, which is released during thrombus formation. The impact of anti-thrombotic agents and the kinetics of platelet angiostatin release are unknown. Hence, our objectives were to characterize platelet angiostatin release temporally and pharmacologically and to determine how angiostatin release influences endothelial cell migration, an early stage of angiogenesis. We hypothesized anti-platelet agents would suppress angiostatin release but not generation by platelets. Human platelets were aggregated and temporal angiostatin release was compared to vascular endothelial growth factor (VEGF). Immuno-gold electron microscopy and immunofluorescence microscopy identified α-granules as storage organelles of platelet angiostatin. Acetylsalicylic acid, MRS2395, GPIIb/IIIa blocking peptide, and aprotinin were used to characterize platelet angiostatin release and generation. An endothelial cell migration assay was performed under hypoxic conditions to determine the effects of pharmacological platelet and angiostatin inhibition. Compared to VEGF, angiostatin generation and release from α-granules occurred later temporally during platelet aggregation. Consequently, collagen-activated platelet releasates stimulated endothelial cell migration more potently than maximally-aggregated platelets. Platelet inhibitors prostacyclin, S-nitroso-glutathione, acetylsalicylic acid, and GPIIb/IIIa blocking peptide, but not a P2Y12 inhibitor, suppressed angiostatin release but not generation. Suppression of angiostatin generation in the presence of acetylsalicylic acid enhanced platelet-stimulated endothelial migration. Hence, the temporal and pharmacological modulation of platelet angiostatin release may have significant consequences for neo-vascularization following thrombus formation. 相似文献
109.
Environmental gradients and wastewater discharges produce aggregated effects on marine populations, obscuring the detection of human impact. Classical assessment methods do not include environmental effects in toxicity tests designs, which could lead to incorrect conclusions. We proposed a modified Whole Effluent Toxicity test (mWET) that includes environmental gradients in addition to effluent dilutions, together with the application of Generalized Linear Mixed Models (GLMM) to assess and decouple those effects. We tested this approach, analyzing the lethal effects of wastewater on a marine sandy beach bivalve affected by an artificial canal freshwater discharge used for rice crops irrigation. To this end, we compared bivalve mortality between canal water dilutions (CWd) and salinity controls (SC: without canal water). CWd were prepared by diluting the water effluent (sampled during the pesticide application period) with artificial marine water. The salinity gradient was included in the design by achieving the same final salinities in both CWd and SC, allowing us to account for the effects of salinity by including this variable as a random factor in the GLMM. Our approach detected significantly higher mortalities in CWd, indicating potential toxic effects of the effluent discharge. mWET represents an improvement over the internationally standardized WET tests, since it considers environmental variability and uses appropriate statistical analyses. 相似文献
110.
Mayra Cuéllar-Cruz Gerardo Gutiérrez-Sánchez Everardo López-Romero Estela Ruiz-Baca Julio C. Villagómez-Castro Lucio Rodríguez-Sifuentes 《Central European Journal of Biology》2013,8(4):337-345
In the past two decades, Candida species have become the second leading cause of invasive mycosis in immunocompromised patients. In order to colonize their hosts, these microorganisms express adhesins and cell wall proteins that allow them to adhere and neutralize the reactive oxygen species produced by phagocytic cells during the respiratory burst. However, the precise mechanism by which Candida cell wall proteins change their expression in response to oxidative stress has not been described. In an attempt to understand this change in response to oxidative stress, in this study, three Candida species, namely, C. albicans, C. glabrata and C. krusei, were exposed to increasing concentrations of H2O2 and induced cell wall proteins were identified by two-dimensional gel electrophoresis and peptide mass fingerprinting. Sequence analysis of differential proteins led to the identification of two heat-shock proteins in C. albicans, two enolases in C. glabrata and one enolase in C. krusei. Enolases may be involved in the protection of pathogenic cells against oxidative stress as suggested by the decrease in their expression when they were exposed to high concentrations of H2O2. To our knowledge, this is the first demonstration that expression of these proteins changes in response to oxidative stress in different Candida species. This knowledge can eventually facilitate both an early diagnosis and a more efficient treatment of this mycosis. 相似文献