全文获取类型
收费全文 | 2198篇 |
免费 | 194篇 |
国内免费 | 4篇 |
专业分类
2396篇 |
出版年
2023年 | 7篇 |
2022年 | 17篇 |
2021年 | 33篇 |
2020年 | 12篇 |
2019年 | 19篇 |
2018年 | 53篇 |
2017年 | 42篇 |
2016年 | 50篇 |
2015年 | 91篇 |
2014年 | 96篇 |
2013年 | 132篇 |
2012年 | 190篇 |
2011年 | 146篇 |
2010年 | 95篇 |
2009年 | 78篇 |
2008年 | 124篇 |
2007年 | 114篇 |
2006年 | 137篇 |
2005年 | 102篇 |
2004年 | 120篇 |
2003年 | 107篇 |
2002年 | 139篇 |
2001年 | 56篇 |
2000年 | 47篇 |
1999年 | 40篇 |
1998年 | 28篇 |
1997年 | 17篇 |
1996年 | 5篇 |
1995年 | 14篇 |
1994年 | 10篇 |
1993年 | 11篇 |
1992年 | 23篇 |
1991年 | 24篇 |
1990年 | 14篇 |
1989年 | 21篇 |
1988年 | 19篇 |
1987年 | 16篇 |
1986年 | 17篇 |
1985年 | 21篇 |
1984年 | 11篇 |
1983年 | 7篇 |
1982年 | 9篇 |
1981年 | 8篇 |
1980年 | 10篇 |
1979年 | 11篇 |
1978年 | 5篇 |
1976年 | 6篇 |
1974年 | 8篇 |
1973年 | 5篇 |
1972年 | 5篇 |
排序方式: 共有2396条查询结果,搜索用时 15 毫秒
61.
Tang CS Cheng G So MT Yip BH Miao XP Wong EH Ngan ES Lui VC Song YQ Chan D Cheung K Yuan ZW Lei L Chung PH Liu XL Wong KK Marshall CR Scherer SW Scherer S Cherny SS Sham PC Tam PK Garcia-Barceló MM 《PLoS genetics》2012,8(5):e1002687
Hirschsprung disease (HSCR) is a congenital disorder characterized by aganglionosis of the distal intestine. To assess the contribution of copy number variants (CNVs) to HSCR, we analysed the data generated from our previous genome-wide association study on HSCR patients, whereby we identified NRG1 as a new HSCR susceptibility locus. Analysis of 129 Chinese patients and 331 ethnically matched controls showed that HSCR patients have a greater burden of rare CNVs (p = 1.50 × 10(-5)), particularly for those encompassing genes (p = 5.00 × 10(-6)). Our study identified 246 rare-genic CNVs exclusive to patients. Among those, we detected a NRG3 deletion (p = 1.64 × 10(-3)). Subsequent follow-up (96 additional patients and 220 controls) on NRG3 revealed 9 deletions (combined p = 3.36 × 10(-5)) and 2 de novo duplications among patients and two deletions among controls. Importantly, NRG3 is a paralog of NRG1. Stratification of patients by presence/absence of HSCR-associated syndromes showed that while syndromic-HSCR patients carried significantly longer CNVs than the non-syndromic or controls (p = 1.50 × 10(-5)), non-syndromic patients were enriched in CNV number when compared to controls (p = 4.00 × 10(-6)) or the syndromic counterpart. Our results suggest a role for NRG3 in HSCR etiology and provide insights into the relative contribution of structural variants in both syndromic and non-syndromic HSCR. This would be the first genome-wide catalog of copy number variants identified in HSCR. 相似文献
62.
Interdependency of sequence and positional specificities for cysteine proteases of the papain family
The specificity of cysteine proteases is characterized by the nature of the amino acid sequence recognized by the enzymes (sequence specificity) as well as by the position of the scissile peptide bond (positional specificity, i.e., endopeptidase, aminopeptidase, or carboxypeptidase). In this paper, the interdependency of sequence and positional specificities for selected members of this class of enzymes has been investigated using fluorogenic substrates where both the position of the cleavable peptide bond and the nature of the sequence of residues in P2-P1 are varied. The results show that cathepsins K and L and papain, typically considered to act strictly as endopeptidases, can also display dipeptidyl carboxypeptidase activity against the substrate Abz-FRF(4NO2)A and dipeptidyl aminopeptidase activity against FR-MCA. In some cases the activity is even equal to or greater than that observed with cathepsin B and DPP-I (dipeptidyl peptidase I), which have been characterized previously as exopeptidases. In contrast, the exopeptidase activities of cathepsins K and L and papain are extremely low when the P2-P1 residues are A-A, indicating that, as observed for the normal endopeptidase activity, the exopeptidase activities rely heavily on interactions in subsite S2 (and possibly S1). However, cathepsin B and DPP-I are able to hydrolyze substrates through the exopeptidase route even in absence of preferred interactions in subsites S2 and S1. This is attributed to the presence in cathepsin B and DPP-I of specific structural elements which serve as an anchor for the C- or N-terminus of a substrate, thereby allowing favorable enzyme-substrate interaction independently of the P2-P1 sequence. As a consequence, the nature of the residue at position P2 of a substrate, which is usually the main factor determining the specificity for cysteine proteases of the papain family, does not have the same contribution for the exopeptidase activities of cathepsin B and DPP-I. 相似文献
63.
64.
Water vapor removal from some simple gases using zeolite NaA was studied by molecular simulation. The equilibrium adsorption properties of H(2)O, CO, H(2), CH(4) and their mixtures in dehydrated zeolite NaA were computed by grand canonical Monte Carlo simulations. The simulations employed Lennard-Jones + Coulomb type effective pair potential models, which are suitable for the reproduction of thermodynamic properties of pure substances. Based on the comparison of the simulation results with experimental data for single-component adsorption at different temperatures and pressures, a modified interaction potential model for the zeolite is proposed. In the adsorption simulations with mixtures presented here, zeolite exhibits extremely high selectivity of water to the investigated weakly polar/non-polar gases demonstrating the excellent dehydration ability of zeolite NaA in engineering applications. 相似文献
65.
66.
Burnett JC Nguyen TL 《Journal of biomolecular structure & dynamics》2011,28(4):641-2; discussion 669-674
67.
Evelin Ramóna Péli Nie Lei Tamás Pócs Zsanett Laufer Stefan Porembski Zoltán Tuba 《Central European Journal of Biology》2011,6(5):838-849
In our present studies, the recovery of photosynthetic activity after rehydration was demonstrated. We measured chlorophyll
fluorescence, CO2 gas exchange and the pigment composition in the previously long-term air-dried cryptogamic inselberg crusts collected from
two tropical areas. The cryptobiotic crusts were collected from different localities on similar ecological and climatic conditions
from extreme habitats of inselbergs (outcrops). These inselbergs are characterized by a dry microclimate and are covered by
scarce soil. We found that the ecophysiological responses of both cryptogamic inselberg crusts showed an extremely high degree
of desiccation-tolerance due to the fast and full recovery during rehydration. The photosynthetic activity of the cryptobiotic
crusts were restored and regained within 15 and 40 min, respectively, after rehydration. Photosynthetic activity of the crusts
was retained at all applied light intensities when enough water was available, however the degree of the recovery was different
between the crusts. Photosynthetic pigment contents were strongly and positively correlated with water content. Our results
indicated that tropical desiccation-tolerant cryptogamic crusts found on inselberg rock surfaces have CO2 fixation ability in the range of cyanobacteria and lichens, suggesting that at a global scale they can assimilate CO2 in a significant amount. 相似文献
68.
Mohan IK Khan M Wisel S Selvendiran K Sridhar A Carnes CA Bognar B Kálai T Hideg K Kuppusamy P 《American journal of physiology. Heart and circulatory physiology》2009,296(1):H140-H151
Many cardiac interventional procedures, such as coronary angioplasty, stenting, and thrombolysis, attempt to reintroduce blood flow (reperfusion) to an ischemic region of myocardium. However, the reperfusion is accompanied by a complex cascade of cellular and molecular events resulting in oxidative damage, termed myocardial ischemia-reperfusion (I/R) injury. In this study, we evaluated the ability of HO-4038, an N-hydroxypiperidine derivative of verapamil, on the modulation of myocardial tissue oxygenation (Po(2)), I/R injury, and key signaling molecules involved in cardioprotection in an in vivo rat model of acute myocardial infarction (MI). MI was created in rats by ligating the left anterior descending coronary artery (LAD) for 30 min followed by 24 h of reperfusion. Verapamil or HO-4038 was infused through the jugular vein 10 min before the induction of ischemia. Myocardial Po(2) and the free-radical scavenging ability of HO-4038 were measured using electron paramagnetic resonance spectroscopy. HO-4038 showed a significantly better scavenging ability of reactive oxygen radicals compared with verapamil. The cardiac contractile functions in the I/R hearts were significantly higher recovery in HO-4038 compared with the verapamil group. A significant decrease in the plasma levels of creatine kinase and lactate dehydrogenase was observed in the HO-4038 group compared with the verapamil or untreated I/R groups. The left ventricular infarct size was significantly less in the HO-4038 (23 +/- 2%) compared with the untreated I/R (36 +/- 4%) group. HO-4038 significantly attenuated the hyperoxygenation (36 +/- 1 mmHg) during reperfusion compared with the untreated I/R group (44 +/- 2 mmHg). The HO-4038-treated group also markedly attenuated superoxide production, increased nitric oxide generation, and enhanced Akt and Bcl-2 levels in the reperfused myocardium. Overall, the results demonstrated that HO-4038 significantly protected hearts against I/R-induced cardiac dysfunction and damage through the combined beneficial actions of calcium-channel blocking, antioxidant, and prosurvival signaling activities. 相似文献
69.
Background
Previous studies show various results obtained from different motif finders for an identical dataset. This is largely due to the fact that these tools use different strategies and possess unique features for discovering the motifs. Hence, using multiple tools and methods has been suggested because the motifs commonly reported by them are more likely to be biologically significant.Results
The common significant motifs from multiple tools can be obtained by using MOTIFSIM tool. In this work, we evaluated the performance of MOTIFSIM in three aspects. First, we compared the pair-wise comparison technique of MOTIFSIM with the un-gapped Smith-Waterman algorithm and four common distance metrics: average Kullback-Leibler, average log-likelihood ratio, Chi-Square distance, and Pearson Correlation Coefficient. Second, we compared the performance of MOTIFSIM with RSAT Matrix-clustering tool for motif clustering. Lastly, we evaluated the performances of nineteen motif finders and the reliability of MOTIFSIM for identifying the common significant motifs from multiple tools.Conclusions
The pair-wise comparison results reveal that MOTIFSIM attains better performance than the un-gapped Smith-Waterman algorithm and four distance metrics. The clustering results also demonstrate that MOTIFSIM achieves similar or even better performance than RSAT Matrix-clustering. Furthermore, the findings indicate if the motif detection does not require a special tool for detecting a specific type of motif then using multiple motif finders and combining with MOTIFSIM for obtaining the common significant motifs, it improved the results for DNA motif detection.70.
W L White S T Tam M S Mitchell M C Yu J Kan-Mitchell 《The journal of histochemistry and cytochemistry》1991,39(6):777-785
Despite the growing list of xenogeneic monoclonal antibodies (MAb) that recognize malignant melanoma-associated antigens (MAA) in formalin-fixed, paraffin-embedded tissue, none has been able to detect epitopes found in malignant melanomas and not in melanocytic nevi. A human MAb, 2-139-1, that showed promise in this regard was evaluated against 85 melanocytic neoplasms, including malignant melanoma and histological simulators, particularly Spitz's nevus. MAb 2-139-1 stained 18 (53%) of 34 melanomas, eight (57%) of 14 dysplastic nevi, six (38%) of 16 Spitz's nevi, and three (14%) of 21 banal nevi, which included three small congenital nevi. We observed a significant increasing trend in reactivity (% positive cells x intensity) associated with the potential for malignancy (p for linear trend = 0.002). We conclude that human MAb 2-139-1 is applicable to the study of melanocytic neoplasms in routinely processed tissue. Although the ability of this MAb to separate benign from malignant cells is not absolute, our results suggest that the expression of the 2-139-1 epitope may be an early event in melanocytic tumor progression. 相似文献