全文获取类型
收费全文 | 2543篇 |
免费 | 249篇 |
国内免费 | 1篇 |
专业分类
2793篇 |
出版年
2022年 | 18篇 |
2021年 | 31篇 |
2019年 | 20篇 |
2018年 | 21篇 |
2017年 | 28篇 |
2016年 | 20篇 |
2015年 | 58篇 |
2014年 | 91篇 |
2013年 | 104篇 |
2012年 | 110篇 |
2011年 | 106篇 |
2010年 | 76篇 |
2009年 | 65篇 |
2008年 | 100篇 |
2007年 | 98篇 |
2006年 | 96篇 |
2005年 | 78篇 |
2004年 | 86篇 |
2003年 | 80篇 |
2002年 | 88篇 |
2001年 | 65篇 |
2000年 | 86篇 |
1999年 | 63篇 |
1998年 | 42篇 |
1997年 | 35篇 |
1996年 | 36篇 |
1995年 | 23篇 |
1994年 | 19篇 |
1993年 | 30篇 |
1992年 | 64篇 |
1991年 | 70篇 |
1990年 | 53篇 |
1989年 | 55篇 |
1988年 | 43篇 |
1987年 | 61篇 |
1986年 | 57篇 |
1985年 | 45篇 |
1984年 | 37篇 |
1983年 | 40篇 |
1982年 | 36篇 |
1981年 | 19篇 |
1979年 | 37篇 |
1978年 | 31篇 |
1977年 | 26篇 |
1976年 | 18篇 |
1974年 | 20篇 |
1973年 | 29篇 |
1970年 | 25篇 |
1969年 | 18篇 |
1968年 | 17篇 |
排序方式: 共有2793条查询结果,搜索用时 562 毫秒
991.
992.
Y Deng J Zhao D Sakurai KM Kaufman JC Edberg RP Kimberly DL Kamen GS Gilkeson CO Jacob RH Scofield CD Langefeld JA Kelly ME Alarcón-Riquelme BIOLUPUS GENLES Networks JB Harley TJ Vyse BI Freedman PM Gaffney KM Sivils JA James TB Niewold RM Cantor W Chen BH Hahn EE Brown PROFILE BP Tsao 《Arthritis research & therapy》2012,14(Z3):A5
993.
Mária Filková Hana Hulejová Klára Kuncová Lenka Ple?tilová Lucie Andrés Cerezo He?man Mann Martin Klein Josef Záme?ník Steffen Gay Ji?í Vencovsky Ladislav ?enolt 《Arthritis research & therapy》2012,14(3):R111-9
Introduction
The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity.Methods
Serum resistin levels were determined in 42 patients with inflammatory myopathies and 27 healthy controls. The association among resistin levels, inflammation, global disease activity and muscle strength was examined. The expression of resistin in muscle tissues from patients with inflammatory myopathies and healthy controls was evaluated. Gene expression and protein release from resistin-stimulated muscle and mononuclear cells were assessed.Results
In patients with inflammatory myopathies, the serum levels of resistin were significantly higher than those observed in controls (8.53 ± 6.84 vs. 4.54 ± 1.08 ng/ml, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r = 0.328, P = 0.044) and myositis disease activity assessment visual analogue scales (MYOACT) (r = 0.382, P = 0.026). Stronger association was observed between the levels of serum resistin and CRP levels (r = 0.717, P = 0.037) as well as MYOACT (r = 0.798, P = 0.007), and there was a trend towards correlation between serum resistin and myoglobin levels (r = 0.650, P = 0.067) in anti-Jo-1 positive patients. Furthermore, in patients with dermatomyositis, serum resistin levels significantly correlated with MYOACT (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with CRP levels (r = 0.447, P = 0.067). Resistin expression in muscle tissue was significantly higher in patients with inflammatory myopathies compared to controls, and resistin induced the expression of interleukins (IL)-1β and IL-6 and monocyte chemoattractant protein (MCP)-1 in mononuclear cells but not in myocytes.Conclusions
The results of this study indicate that higher levels of serum resistin are associated with inflammation, higher global disease activity index and muscle injury in patients with myositis-specific anti-Jo-1 antibody and patients with dermatomyositis. Furthermore, up-regulation of resistin in muscle tissue and resistin-induced synthesis of pro-inflammatory cytokines in mononuclear cells suggest a potential role for resistin in the pathogenesis of inflammatory myopathies. 相似文献994.
995.
A framework for intelligent data acquisition and real-time database searching for shotgun proteomics
Graumann J Scheltema RA Zhang Y Cox J Mann M 《Molecular & cellular proteomics : MCP》2012,11(3):M111.013185
In the analysis of complex peptide mixtures by MS-based proteomics, many more peptides elute at any given time than can be identified and quantified by the mass spectrometer. This makes it desirable to optimally allocate peptide sequencing and narrow mass range quantification events. In computer science, intelligent agents are frequently used to make autonomous decisions in complex environments. Here we develop and describe a framework for intelligent data acquisition and real-time database searching and showcase selected examples. The intelligent agent is implemented in the MaxQuant computational proteomics environment, termed MaxQuant Real-Time. It analyzes data as it is acquired on the mass spectrometer, constructs isotope patterns and SILAC pair information as well as controls MS and tandem MS events based on real-time and prior MS data or external knowledge. Re-implementing a top10 method in the intelligent agent yields similar performance to the data dependent methods running on the mass spectrometer itself. We demonstrate the capabilities of MaxQuant Real-Time by creating a real-time search engine capable of identifying peptides "on-the-fly" within 30 ms, well within the time constraints of a shotgun fragmentation "topN" method. The agent can focus sequencing events onto peptides of specific interest, such as those originating from a specific gene ontology (GO) term, or peptides that are likely modified versions of already identified peptides. Finally, we demonstrate enhanced quantification of SILAC pairs whose ratios were poorly defined in survey spectra. MaxQuant Real-Time is flexible and can be applied to a large number of scenarios that would benefit from intelligent, directed data acquisition. Our framework should be especially useful for new instrument types, such as the quadrupole-Orbitrap, that are currently becoming available. 相似文献
996.
997.
In terms of its soluble precursors, the coagulation proteome varies quantitatively among apparently healthy individuals. The significance of this variability remains obscure, in part because it is the backdrop against which the hemostatic consequences of more dramatic composition differences are studied. In this study we have defined the consequences of normal range variation of components of the coagulation proteome by using a mechanism-based computational approach that translates coagulation factor concentration data into a representation of an individual's thrombin generation potential. A novel graphical method is used to integrate standard measures that characterize thrombin generation in both empirical and computational models (e.g max rate, max level, total thrombin, time to 2 nM thrombin ("clot time")) to visualize how normal range variation in coagulation factors results in unique thrombin generation phenotypes. Unique ensembles of the 8 coagulation factors encompassing the limits of normal range variation were used as initial conditions for the computational modeling, each ensemble representing "an individual" in a theoretical healthy population. These "individuals" with unremarkable proteome composition was then compared to actual normal and "abnormal" individuals, i.e. factor ensembles measured in apparently healthy individuals, actual coagulopathic individuals or artificially constructed factor ensembles representing individuals with specific factor deficiencies. A sensitivity analysis was performed to rank either individual factors or all possible pairs of factors in terms of their contribution to the overall distribution of thrombin generation phenotypes. Key findings of these analyses include: normal range variation of coagulation factors yields thrombin generation phenotypes indistinguishable from individuals with some, but not all, coagulopathies examined; coordinate variation of certain pairs of factors within their normal ranges disproportionately results in extreme thrombin generation phenotypes, implying that measurement of a smaller set of factors may be sufficient to identify individuals with aberrant thrombin generation potential despite normal coagulation proteome composition. 相似文献
998.
The newly developed multireceptor somatostatin analogs pasireotide (SOM230), octreotide and somatoprim (DG3173) have primarily been characterized according to their binding profiles. However, their ability to activate individual somatostatin receptor subtypes (sst) has not been directly assessed so far. Here, we transplanted the carboxyl-terminal phosphorylation motif of the sst(2) receptor to other somatostatin receptors and assessed receptor activation using a set of three phosphosite-specific antibodies. Our comparative analysis revealed unexpected efficacy profiles for pasireotide, octreotide and somatoprim. Pasireotide was able to activate sst(3) and sst(5) receptors but was only a partial agonist at the sst(2) receptor. Octreotide exhibited potent agonistic properties at the sst(2) receptor but produced very little sst(5) receptor activation. Like octreotide, somatoprim was a full agonist at the sst(2) receptor. Unlike octreotide, somatoprim was also a potent agonist at the sst(5) receptor. Together, we propose the application of a phosphorylation probe for direct assessment of G protein-coupled receptor activation and demonstrate its utility in the pharmacological characterization of novel somatostatin analogs. 相似文献
999.
cGametogenesis and auxospore development have been studied in detail in surprisingly few centric diatoms. We studied the development of sperm, eggs and auxospores in Actinocyclus sp., a radially symmetrical freshwater diatom collected from Japan, using LM and electron microscopy of living cultures and thin sections. Actinocyclus represents a deep branch of the 'radial centric' diatoms and should therefore contribute useful insights into the evolution of sexual reproduction in diatoms. Spermatogenesis was examined by LM and SEM and involved the formation of two spermatogonia (sperm mother-cells) in each spermatogonangium through an equal mitotic division. The spermatogonia produced a reduced 'lid' valve, resembling a large flat scale with irregular radial thickenings. Sperm formation was merogenous, producing four sperm per spermatogonium, which were released by dehiscence of the 'lid' valve. The sperm were spindle-shaped with numerous surface globules and, as usual for diatoms, the single anterior flagellum bore mastigonemes. One egg cell was produced per oogonium. Immature eggs produced a thin layer of circular silica scales before fertilization, while the eggs were still contained within the oogonium. Sperm were attracted in large numbers to each egg and were apparently able to contact the egg surface via a gap formed between the long hypotheca and shorter epitheca of the oogonium and a small underlying hole in the scale-case. Auxospores expanded isodiametrically and many new scales were added to its envelope during expansion. Finally, new slightly-domed initial valves were produced at right angles to the oogonium axis, after a strong contraction of the cell away from the auxospore wall. At different stages, Golgi bodies were associated with chloroplasts or mitochondria, contrasting with the constancy of Golgi-ER-mitochondrion (G-ER-M) units in some other centric diatoms, which has been suggested to have phylogenetic significance. Electron-dense bodies in the vacuole of Actinocyclus are probably acidocalcisomes containing polyphosphate. 相似文献
1000.