全文获取类型
收费全文 | 15582篇 |
免费 | 1537篇 |
国内免费 | 2篇 |
专业分类
17121篇 |
出版年
2024年 | 16篇 |
2023年 | 97篇 |
2022年 | 217篇 |
2021年 | 376篇 |
2020年 | 233篇 |
2019年 | 272篇 |
2018年 | 325篇 |
2017年 | 295篇 |
2016年 | 506篇 |
2015年 | 954篇 |
2014年 | 923篇 |
2013年 | 1127篇 |
2012年 | 1469篇 |
2011年 | 1404篇 |
2010年 | 894篇 |
2009年 | 767篇 |
2008年 | 996篇 |
2007年 | 993篇 |
2006年 | 947篇 |
2005年 | 903篇 |
2004年 | 859篇 |
2003年 | 739篇 |
2002年 | 681篇 |
2001年 | 112篇 |
2000年 | 70篇 |
1999年 | 113篇 |
1998年 | 135篇 |
1997年 | 76篇 |
1996年 | 71篇 |
1995年 | 55篇 |
1994年 | 54篇 |
1993年 | 53篇 |
1992年 | 36篇 |
1991年 | 45篇 |
1990年 | 30篇 |
1989年 | 16篇 |
1988年 | 31篇 |
1987年 | 15篇 |
1986年 | 16篇 |
1985年 | 18篇 |
1984年 | 14篇 |
1983年 | 17篇 |
1982年 | 20篇 |
1981年 | 12篇 |
1980年 | 16篇 |
1979年 | 7篇 |
1978年 | 11篇 |
1977年 | 14篇 |
1976年 | 7篇 |
1974年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
The mammalian pacemaker in the suprachiasmatic nucleus (SCN) contains a population of neural oscillators capable of sustaining cell-autonomous rhythms in gene expression and electrical firing. A critical question for understanding pacemaker function is how SCN oscillators are organized into a coherent tissue capable of coordinating circadian rhythms in behavior and physiology. Here we undertake a comprehensive analysis of oscillatory function across the SCN of the adult PER2::LUC mouse by developing a novel approach involving multi-position bioluminescence imaging and unbiased computational analyses. We demonstrate that there is phase heterogeneity across all three dimensions of the SCN that is intrinsically regulated and extrinsically modulated by light in a region-specific manner. By investigating the mechanistic bases of SCN phase heterogeneity, we show for the first time that phase differences are not systematically related to regional differences in period, waveform, amplitude, or brightness. Furthermore, phase differences are not related to regional differences in the expression of arginine vasopressin and vasoactive intestinal polypeptide, two key neuropeptides characterizing functionally distinct subdivisions of the SCN. The consistency of SCN spatiotemporal organization across individuals and across planes of section suggests that the precise phasing of oscillators is a robust feature of the pacemaker important for its function. 相似文献
102.
The claim that the herbicide Diuron in agricultural runoff caused dieback of the grey mangrove (Avicennia marina) in Central Queensland, Australia, has influenced government policies including programs to save the Great Barrier Reef. Several investigations on mangrove dieback in Central Queensland river estuaries have been published during the past decade. However, proof of a causal link between mangrove dieback and Diuron remains inconclusive. This study presents a systematic review of the evidence using Hill's Criteria of Causation. Our review shows that using concentrations of the chemical bound to sediment as a measure for biological availability in either glasshouse or field studies is inappropriate. The appropriate measure is Diuron concentration in solution and this parameter bears no simple relationship to concentration bound to sediment, and is not strongly correlated with mangrove health. Only when the herbicide is applied in experimental investigations at many orders of magnitude higher than measured in rivers has an impact on A. marina been demonstrated. Evidence from field studies suggests burial of pneumatophores, the plant's breathing roots, following flood events is a more likely causal factor in mangrove dieback, whereas any contribution from Diuron remains unproven. 相似文献
103.
104.
Kerstin Reiss Jennifer E. Stencel Yan Liu B?rbel S. Blaum Dirk M. Reiter Ten Feizi Terence S. Dermody Thilo Stehle 《PLoS pathogens》2012,8(12)
Viral attachment to target cells is the first step in infection and also serves as a determinant of tropism. Like many viruses, mammalian reoviruses bind with low affinity to cell-surface carbohydrate receptors to initiate the infectious process. Reoviruses disseminate with serotype-specific tropism in the host, which may be explained by differential glycan utilization. Although α2,3-linked sialylated oligosaccharides serve as carbohydrate receptors for type 3 reoviruses, neither a specific glycan bound by any reovirus serotype nor the function of glycan binding in type 1 reovirus infection was known. We have identified the oligosaccharide portion of ganglioside GM2 (the GM2 glycan) as a receptor for the attachment protein σ1 of reovirus strain type 1 Lang (T1L) using glycan array screening. The interaction of T1L σ1 with GM2 in solution was confirmed using NMR spectroscopy. We established that GM2 glycan engagement is required for optimal infection of mouse embryonic fibroblasts (MEFs) by T1L. Preincubation with GM2 specifically inhibited type 1 but not type 3 reovirus infection of MEFs. To provide a structural basis for these observations, we defined the mode of receptor recognition by determining the crystal structure of T1L σ1 in complex with the GM2 glycan. GM2 binds in a shallow groove in the globular head domain of T1L σ1. Both terminal sugar moieties of the GM2 glycan, N-acetylneuraminic acid and N-acetylgalactosamine, form contacts with the protein, providing an explanation for the observed specificity for GM2. Viruses with mutations in the glycan-binding domain display diminished hemagglutination capacity, a property dependent on glycan binding, and reduced capacity to infect MEFs. Our results define a novel mode of virus-glycan engagement and provide a mechanistic explanation for the serotype-dependent differences in glycan utilization by reovirus. 相似文献
105.
Jones LL Colf LA Stone JD Garcia KC Kranz DM 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(9):6255-6264
T cells are known to cross-react with diverse peptide MHC Ags through their alphabeta TCR. To explore the basis of such cross-reactivity, we examined the 2C TCR that recognizes two structurally distinct ligands, SIY-K(b) and alloantigen QL9-L(d). In this study we characterized the cross-reactivity of several high-affinity 2C TCR variants that contained mutations only in the CDR3alpha loop. Two of the TCR lost their ability to cross-react with the reciprocal ligand (SIY-K(b)), whereas another TCR (m67) maintained reactivity with both ligands. Crystal structures of four of the TCRs in complex with QL9-L(d) showed that CDR1, CDR2, and CDR3beta conformations and docking orientations were remarkably similar. Although the CDR3alpha loop of TCR m67 conferred a 2000-fold higher affinity for SIY-K(b), the TCR maintained the same docking angle on QL9-L(d) as the 2C TCR. Thus, CDR3alpha dictated the affinity and level of cross-reactivity, yet it did so without affecting the conserved docking orientation. 相似文献
106.
107.
108.
Lisa A. Ridnour Sneha Dhanapal Michael Hoos Joan Wilson Jennifer Lee Robert Y. S. Cheng Ernst E. Brueggemann Harry B. Hines Donna M. Wilcock Michael P. Vitek David A. Wink Carol A. Colton 《Journal of neurochemistry》2012,123(5):736-749
Fibrillar amyloid plaques are largely composed of amyloid‐beta (Aβ) peptides that are metabolized into products, including Aβ1‐16, by proteases including matrix metalloproteinase 9 (MMP‐9). The balance between production and degradation of Aβ proteins is critical to amyloid accumulation and resulting disease. Regulation of MMP‐9 and its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP)‐1 by nitric oxide (NO) has been shown. We hypothesize that nitric oxide synthase (NOS2) protects against Alzheimer's disease pathology by increasing amyloid clearance through NO regulation of MMP‐9/TIMP‐1 balance. We show NO‐mediated increased MMP‐9/TIMP‐1 ratios enhanced the degradation of fibrillar Aβ in vitro, which was abolished when silenced for MMP‐9 protein translation. The in vivo relationship between MMP‐9, NO and Aβ degradation was examined by comparing an Alzheimer's disease mouse model that expresses NOS2 with a model lacking NOS2. To quantitate MMP‐9 mediated changes, we generated an antibody recognizing the Aβ1‐16 fragment, and used mass spectrometry multi‐reaction monitoring assay for detection of immunoprecipitated Aβ1‐16 peptides. Aβ1‐16 levels decreased in brain lysates lacking NOS2 when compared with strains that express human amyloid precursor protein on the NOS2 background. TIMP‐1 increased in the APPSwDI/NOS2?/? mice with decreased MMP activity and increased amyloid burden, thereby supporting roles for NO in the regulation of MMP/TIMP balance and plaque clearance. 相似文献
109.
Schistosomiasis and hydration status: Schistosoma haematobium,but not Schistosoma mansoni increases urine specific gravity among rural Tanzanian women 下载免费PDF全文