全文获取类型
收费全文 | 7089篇 |
免费 | 494篇 |
专业分类
7583篇 |
出版年
2024年 | 4篇 |
2023年 | 36篇 |
2022年 | 103篇 |
2021年 | 193篇 |
2020年 | 104篇 |
2019年 | 132篇 |
2018年 | 195篇 |
2017年 | 178篇 |
2016年 | 266篇 |
2015年 | 389篇 |
2014年 | 439篇 |
2013年 | 544篇 |
2012年 | 712篇 |
2011年 | 654篇 |
2010年 | 387篇 |
2009年 | 352篇 |
2008年 | 457篇 |
2007年 | 425篇 |
2006年 | 378篇 |
2005年 | 355篇 |
2004年 | 297篇 |
2003年 | 271篇 |
2002年 | 236篇 |
2001年 | 36篇 |
2000年 | 36篇 |
1999年 | 51篇 |
1998年 | 50篇 |
1997年 | 32篇 |
1996年 | 34篇 |
1995年 | 28篇 |
1994年 | 24篇 |
1993年 | 19篇 |
1992年 | 21篇 |
1991年 | 13篇 |
1990年 | 12篇 |
1989年 | 15篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 13篇 |
1983年 | 9篇 |
1982年 | 5篇 |
1981年 | 8篇 |
1980年 | 8篇 |
1979年 | 8篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1973年 | 3篇 |
1967年 | 3篇 |
排序方式: 共有7583条查询结果,搜索用时 10 毫秒
941.
ABSTRACT: BACKGROUND: An approach to molecular classification based on the comparative expression of protein pairs is presented.The method overcomes some of the present limitations in using peptide intensity data for class prediction forproblems such as the detection of a disease, disease prognosis, or for predicting treatment response. Dataanalysis is particularly challenging in these situations due to sample size (typically tens) being much smallerthan the large number of peptides (typically thousands). Methods based upon high dimensional statisticalmodels, machine learning or other complex classifiers generate decisions which may be very accurate butcan be complex and difficult to interpret in simple or biologically meaningful terms. A classificationscheme, called ProtPair, is presented that generates simple decision rules leading to accurate classificationwhich is based on measurement of very few proteins and requires only relative expression values, providingspecific targeted hypotheses suitable for straightforward validation. RESULTS: ProtPair has been tested against clinical data from 21 patients following a bone marrow transplant, 13 ofwhich progress to idiopathic pneumonia syndrome (IPS). The approach combines multiple peptide pairsoriginating from the same set of proteins, with each unique peptide pair providing an independent measureof discriminatory power. The prediction rate of the ProtPair for IPS study as measured by leave-one-out CVis 69.1%, which can be very beneficial for clinical diagnosis as it may flag patients in need of closer monitoring. The "top ranked" proteins provided by ProtPair are known to be associated with the biologicalprocesses and pathways intimately associated with known IPS biology based on mouse models. CONCLUSIONS: An approach to biomarker discovery, called ProtPair, is presented. ProtPair is based on the differentialexpression of pairs of peptides and the associated proteins. Using mass spectrometry data from "bottom up"proteomics methods, functionally related proteins/peptide pairs exhibiting co-ordinated changes expressionprofile are discovered, which represent a signature for patients progressing to various disease conditions.The method has been tested against clinical data from patients progressing to idiopthatic pneumoniasyndrome (IPS) following a bone marrow transplant. The data indicates that patients with improperregulation in the concentration of specific acute phase response proteins at the time of bone marrowtransplant are highly likely to develop IPS within few weeks. The results lead to a specific set of proteinpairs that can be efficiently verified by investigating the pairwise abundance change in independent cohortsusing ELISA or targeted mass spectrometry techniques. This generalized classifier can be extended to otherclinical problems in a variety of contexts. 相似文献
942.
Wiese C Rudolph JH Jakob B Fink D Tobias F Blattner C Taucher-Scholz G 《DNA Repair》2012,11(5):511-521
The cyclin-dependent kinase inhibitor CDKN1A/p21 confers cell-cycle arrest in response to DNA damage and inhibits DNA replication through its direct interaction with the proliferating cell nuclear antigen (PCNA) and cyclin/cyclin-dependent kinase complexes. Previously, we reported that in response to densely ionizing radiation CDKN1A rapidly is recruited to the sites of particle traversal, and that CDKN1A foci formation in response to heavy ions is independent of its transactivation by TP53. Here, we show that exposure of normal human fibroblasts to X-rays or to H2O2 also induces nuclear accumulations of CDKN1A. We find that CDKN1A foci formation in response to radiation damage is dependent on its dephosphorylation and on its direct physical interaction with PCNA. Live cell imaging analyses of ectopically expressed EGFP-CDKN1A and dsRed-PCNA show rapid recruitment of both proteins into foci after radiation damage. Detailed dynamic measurements reveal a slightly delayed recruitment of CDKN1A compared to PCNA, which is best described by bi-exponential curve fitting, taking the preceding binding of PCNA to DNA into account. We propose a regulatory role for CDKN1A in mediating PCNA function after radiation damage, and provide evidence that this role is distinct from its involvement in nucleotide excision repair and unrelated to double-strand break repair. 相似文献
943.
Souza Vdo C Schlemmer KB Noal CB Jaques JA Bagatini MD Pimentel VC Carli LF Leal CA Fleck J Moretto MB Schetinger MR Leal DB 《Purinergic signalling》2012,8(4):753-762
Chagas disease (CD) is a chronic and endemic illness caused by the parasite Trypanosoma cruzi. Microvascular disturbances play an important role in the progress of the disease. The purinergic signaling system participates in regulatory functions, such as immunomodulation, neuroprotection, and thromboregulation. This study aimed to investigate the activities of purinergic system ecto-enzymes present on the platelet surface and the platelet aggregation profile from patients with indeterminate form of Chagas disease (IFCD). Thirty patients diagnosed with IFCD and 30 healthy subjects were selected. Ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP), ecto-5′-nucleotidase (E-5′-NT) and ecto-adenosine deaminase (E-ADA) activities were measured in platelets isolated from these individuals as well as the platelet aggregation. Results demonstrated an increase of 21 % in the E-NPP activity and 30 % in the E-5′-NT activity in IFCD group (P < 0.05); however, a decrease of 34 % in the E-ADA activity was determined in the same group (P < 0.001). A significant decrease of 12.7 % and 12.8 % in the platelet aggregation of IFCD group in two different concentrations of ADP (5 and 10 μM) was observed, respectively (P < 0.05). Increased E-NPP and E-5-NT activities as well as decreased E-ADA activity in platelets of patients with IFCD contributed to decrease platelet aggregation, suggesting that the purinergic system is involved in the thromboregulation process in these patients, since adenosine (the final product of ATP hydrolysis) has cardioprotective and vasodilator effects that prevent the clinical progress of the disease. 相似文献
944.
Carmen Formisano Daniela Rigano Felice Senatore Svetlana Bancheva Antonella Maggio Sergio Rosselli Maurizio Bruno 《化学与生物多样性》2012,9(10):2096-2158
This review reports the occurrence of flavonoids in subtribe Centaureinae of Asteraceae family. It extensively covers the literature up to 2010 and collects all available 13C‐NMR data. 相似文献
945.
Software advancements in the last several years have had a significant impact on proteomics from method development to data analysis. Herein, we detail a method, which uses our in-house developed software tool termed Skyline, for empirical refinement of candidate peptides from targeted proteins. The method consists of four main steps from generation of a testable hypothesis, method development, peptide refinement, to peptide validation. The ultimate goal is to identify the best performing peptide in terms of ionization efficiency, reproducibility, specificity, and chromatographic characteristics to monitor as a proxy for protein abundance. It is important to emphasize that this method allows the user to perform this refinement procedure in the sample matrix and organism of interest with the instrumentation available. Finally, the method is demonstrated in a case study to determine the best peptide to monitor the abundance of surfactant protein B in lung aspirates. 相似文献
946.
Pitarresi G Triolo D Giorgi M Fiorica C Calascibetta F Giammona G 《Macromolecular bioscience》2012,12(6):770-778
The ability of a hydrogel obtained by crosslinking INUDV and PEGBa to facilitate sustained release of flutamide is examined. The hydrogel is prepared in pH?=?7.4 PBS and no toxic solvents or catalysts are used. It is recovered in microparticulate form and its size distribution is determined. Mucoadhesive properties are evaluated in vitro by reproducing gastrointestinal conditions. Flutamide is loaded into the hydrogel using a post-fabrication encapsulation procedure that allows a drug loading comparable to that of market tablets. Drug-loaded microparticles are orally administered to cross-bred dogs and the in vivo study demonstrates their ability to prolong the half-life of the principal active metabolite approximately threefold and to significantly increase its bioavailability. 相似文献
947.
Monje FJ Birner-Gruenberger R Darnhofer B Divisch I Pollak DD Lubec G 《Proteomics》2012,12(3):490-499
The marine mollusk Aplysia californica (Aplysia) is a powerful model for learning and memory due to its minimalistic nervous system. Key proteins, identified to be regulated by the neurotransmitter serotonin in Aplysia, have been successfully translated to mammalian models of learning and memory. Based upon a recently published large‐scale analysis of Aplysia proteomic data, the current study investigated the regulation of protein levels 24 and 48 h after treatment with serotonin in Aplysia ganglia using a 2‐D gel electrophoresis approach. Protein spots were quantified and protein‐level changes of selected proteins were verified by Western blotting. Among those were Rab GDP dissociation inhibitor alpha (RabGDIα), synaptotagmin‐1 and deleted in azoospermia‐associated protein (DAZAP‐1) in cerebral ganglia, calreticulin, RabGDIα, DAZAP‐1, heterogeneous nuclear ribonucleoprotein F (hnRNPF), RACK‐1 and actin‐depolymerizing factor (ADF) in pleural ganglia and DAZAP‐1, hnRNPF and ADF in pedal ganglia. Protein identity of the majority of spots was confirmed by a gel‐based mass spectrometrical method (FT‐MS). Taken together, protein‐level changes induced by the learning‐related neurotransmitter serotonin in Aplysia ganglia are described and a role for the abovementioned proteins in synaptic plasticity is proposed. 相似文献
948.
D Marone G Panio DB Ficco MA Russo P De Vita R Papa D Rubiales L Cattivelli AM Mastrangelo 《Molecular genetics and genomics : MGG》2012,287(9):741-753
Diversity array technology (DArT) markers are largely used for mapping, genetic diversity, and association mapping studies. For years, they have been used as anonymous genomic markers, as their sequences were not known. As the sequences of 2,000 wheat DArT clones are now available, this study was designed to analyze these sequences with bioinformatic approaches, and to study the genetic features of a subset of 291 markers positioned on the A and B genomes in three durum wheat genetic maps. A set of 1,757 non-redundant sequences was identified, and used as queries for similarity searches. Analysis of the genetic positions of markers corresponding to nearly identical sequences indicates that redundancy of sequences is one of the factors that explains the clustering of these markers in specific genomic regions. Of a total of 1,124 DArT clones (64?%) that represent putatively expressed sequences, putative functions are proposed for more than 700 of them. Of note, many clones correspond to genes that are related to disease resistance, as characterized by leucine-rich repeat domains, and 40 of these clones are positioned in the three genetic maps presented in this study. Finally, DArT markers have been used to find syntenic regions in the Brachypodium and rice genomes. In conclusion, the analyses herein presented contribute to explain the main features of DArT markers observed in genetic maps, as clustering in short chromosome regions. Moreover, the attribution of putative gene functions for more than 700 sequences makes these markers an optimal tool for collinearity studies or for the identification of candidate genes. 相似文献
949.
Alburnus alburnus alborella is a fish species native to northern Italy. It has suffered a very sharp decrease in population over the last 20 years due to human impact. Therefore, it was selected for reintroduction projects. In this research project, support vector machines (SVM) were tested as possible tools for building reliable models of presence/absence of the species. A system of 198 sites located along the rivers of Piedmont in North-Western Italy was investigated. At each site, 19 physical-chemical and environmental variables were measured. We verified that performances did not improve after feature selection but, instead, they slightly decreased (from Correctly Classified Instances [CCI] = 84.34 and Cohen's k [k] = 0.69 to CCI = 82.81 and k = 0.66). However, feature selection is crucial in identifying the relevant features for the presence/absence of the species. We then compared SVMs performances with decision trees (DTs) and artificial neural networks (ANNs) built using the same dataset. SVMs outperformed DTs (CCI = 81.39 and k = 0.63) but not ANNs (CCI = 83.03 and k = 0.66), showing that SVMs and ANNs are the best performing models, proving that their application in freshwater management is more promising than traditional and other machine-learning techniques. 相似文献
950.
Morna Cornell Michael Schomaker Daniela Belen Garone Janet Giddy Christopher J. Hoffmann Richard Lessells Mhairi Maskew Hans Prozesky Robin Wood Leigh F. Johnson Matthias Egger Andrew Boulle Landon Myer for the International Epidemiologic Databases to Evaluate AIDS Southern Africa Collaboration 《PLoS medicine》2012,9(9)