全文获取类型
收费全文 | 1142篇 |
免费 | 64篇 |
专业分类
1206篇 |
出版年
2024年 | 2篇 |
2023年 | 13篇 |
2022年 | 33篇 |
2021年 | 50篇 |
2020年 | 31篇 |
2019年 | 35篇 |
2018年 | 45篇 |
2017年 | 43篇 |
2016年 | 54篇 |
2015年 | 80篇 |
2014年 | 82篇 |
2013年 | 99篇 |
2012年 | 84篇 |
2011年 | 75篇 |
2010年 | 38篇 |
2009年 | 47篇 |
2008年 | 44篇 |
2007年 | 55篇 |
2006年 | 53篇 |
2005年 | 44篇 |
2004年 | 28篇 |
2003年 | 32篇 |
2002年 | 24篇 |
2001年 | 23篇 |
2000年 | 6篇 |
1999年 | 14篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 7篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1982年 | 2篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1965年 | 1篇 |
1941年 | 1篇 |
1940年 | 1篇 |
1903年 | 1篇 |
排序方式: 共有1206条查询结果,搜索用时 10 毫秒
51.
52.
Structural and functional characterization of N-terminally blocked peptides isolated from the venom of the social wasp Polybia paulista 总被引:2,自引:0,他引:2
Ribeiro SP Mendes MA Dos Santos LD de Souza BM Marques MR de Azevedo WF Palma MS 《Peptides》2004,25(12):2069-2078
Two novel peptides were isolated from the crude venom of the social wasp Polybia paulista, by using RP-HPLC under a gradient of MeCN from 5 to 60% (v/v) and named Polybine-I and -II. Further purification of these peptides under normal phase chromatography, rendered pure enough preparations to be sequenced by Edman degradation chemistry. However, both peptides did not interact with phenylisothiocyanate reagent, suggesting the existence of a chemically blocked N-terminus. Therefore, the sequences of both peptides were assigned by ESI-MS/MS under CID conditions, as follows: Polybine-I Ac-SADLVKKIWDNPAL-NH2 (Mr 1610 Da) and Polybine-II Ac-SVDMVMKGLKIWPL-NH2 (Mr 1657 Da). During the tandem mass spectrometry experiments, a loss of 43 a.m.u. was observed from the N-terminal residue of each peptide, suggesting the acetylation of the N-terminus. Subsequently, the peptides with and without acetylation were synthesized on solid phase and submitted to functional characterizations; the biological activities investigated were: hemolysis, chemotaxis of polymorphonucleated leukocytes (PMNL), mast cell degranulation and antibiosis. The results revealed that the acetylated peptides exhibited more pronounced chemotaxis of PMNL cells and mast cell degranulation than the respective non-acetylated congeners; no hemolytic and antibiotic activities were observed, irrespective to the blockage or not of the -amino groups of the N-terminal residues of each peptide. Therefore, the N-terminal acetylation may be related to the increase of the inflammatory activity of both peptides. 相似文献
53.
Araújo-Jorge TC Cardona TS Mendes CL Henriques-Pons A Meirelles RM Coutinho CM Aguiar LE Meirelles Mde N de Castro SL Barbosa HS Luz MR 《Cell biology education》2004,3(2):99-110
The advent of genomics, proteomics, and microarray technology has brought much excitement to science, both in teaching and in learning. The public is eager to know about the processes of life. In the present context of the explosive growth of scientific information, a major challenge of modern cell biology is to popularize basic concepts of structures and functions of living cells, to introduce people to the scientific method, to stimulate inquiry, and to analyze and synthesize concepts and paradigms. In this essay we present our experience in mixing science and education in Brazil. For two decades we have developed activities for the science education of teachers and undergraduate students, using microscopy images generated by our work as cell biologists. We describe open-air outreach education activities, games, cell modeling, and other practical and innovative activities presented in public squares and favelas. Especially in developing countries, science education is important, since it may lead to an improvement in quality of life while advancing understanding of traditional scientific ideas. We show that teaching and research can be mutually beneficial rather than competing pursuits in advancing these goals. 相似文献
54.
Lisinopril quantification in human plasma by liquid chromatography-electrospray tandem mass spectrometry 总被引:4,自引:0,他引:4
Padua AA Barrientos-Astigarraga RE Rezende VM Mendes GD De Nucci G 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,809(2):211-216
An analytical method based on liquid chromatography with positive ion electrospray ionization (ESI) coupled to tandem mass spectrometry detection was developed for the determination of Lisinopril in human plasma using Enalaprilat as internal standard. The analyte and internal standard were extracted from the plasma samples by solid-phase extraction using Waters HLB Oasis SPE cartridges and chromatographed on a C8 analytical column. The mobile phase consisted of acetonitrile/water (60:40, v/v) + 20 mM acetic acid + 4.3 mM of triethylamine. The method had a chromatographic total run-time of 6.5 min and was linear within the range 2.00-200 ng/ml. Detection was carried out on a Micromass triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM). The precision (CV%) and accuracy, calculated from limit of quantification (LOQ) samples (n = 8), were 8.9 and 98.9%, respectively. The method herein described was employed in a bioequivalence study of two tablet formulations of Lisinopril 20mg. 相似文献
55.
Kenney MJ Weiss ML Mendes T Wang Y Fels RJ 《American journal of physiology. Heart and circulatory physiology》2003,284(5):H1710-H1720
Autospectral and coherence analyses were used to determine the role of and interactions between paraventricular nucleus (PVN) nitric oxide, gamma-aminobutyric acid (GABA), and the N-methyl-D-aspartic acid (NMDA)-glutamate receptor in regulation of sympathetic nerve discharge (SND) frequency components in anesthetized rats. Four observations were made. First, PVN microinjection of bicuculline (BIC) (GABA(A) receptor antagonist), but not single PVN injections of NMDA (excitatory amino acid) or N(G)-monomethyl-L-arginine (L-NMMA; a nitric oxide synthase inhibitor), altered SND frequency components. Second, combined PVN microinjections of L-NMMA and NMDA changed the SND bursting pattern; however, the observed pattern change was different from that produced by PVN BIC and not observed after sinoaortic denervation. Third, PVN microinjection of kynurenic acid prevented and reversed BIC-induced changes in the SND bursting pattern. Finally, vascular resistance (renal and splenic) was significantly increased after PVN BIC microinjection despite the lack of change in the level of renal and splenic SND. These data demonstrate that the PVN contains the neural substrate for altering SND frequency components and suggest complex interactions between specific PVN neurotransmitters and between PVN neurotransmitters and the arterial baroreceptor reflex in SND regulation. 相似文献
56.
Filgueira de Azevedo W dos Santos GC dos Santos DM Olivieri JR Canduri F Silva RG Basso LA Renard G da Fonseca IO Mendes MA Palma MS Santos DS 《Biochemical and biophysical research communications》2003,309(4):923-928
Docking simulations have been used to assess protein complexes with some success. Small angle X-ray scattering (SAXS) is a well-established technique to investigate protein spatial configuration. This work describes the integration of geometric docking with SAXS to investigate the quaternary structure of recombinant human purine nucleoside phosphorylase (PNP). This enzyme catalyzes the reversible phosphorolysis of N-ribosidic bonds of purine nucleosides and deoxynucleosides. A genetic deficiency due to mutations in the gene encoding for PNP causes gradual decrease in T-cell immunity. Inappropriate activation of T-cells has been implicated in several clinically relevant human conditions such as transplant rejection, rheumatoid arthritis, lupus, and T-cell lymphomas. PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. The present analysis confirms the trimeric structure observed in the crystal. The potential application of the present procedure to other systems is discussed. 相似文献
57.
A correspondence is established between the basic elements of logic reasoning systems (knowledge bases, rules, inference and queries) and the structure and dynamical evolution laws of neural networks. The correspondence is pictured as a translation dictionary which might allow to go back and forth between symbolic and network formulations, a desirable step in learning-oriented systems and multicomputer networks. In the framework of Horn clause logics, it is found that atomic propositions with n arguments correspond to nodes with nth order synapses, rules to synaptic intensity constraints, forward chaining to synaptic dynamics and queries either to simple node activation or to a query tensor dynamics. 相似文献
58.
de Oliveira LC Ribeiro CT Mendes Dde M Oliveira TC Costa-Cruz JM 《Memórias do Instituto Oswaldo Cruz》2002,97(1):119-121
Several studies have shown that chronic alcoholics have increased susceptibility to infections due to higher exposure to infectious agents as well as breakdown in their immune defenses. As Strongyloides stercoralis infection is usually more relevant in immunocompromised patients, the aim of this study was to evaluate the frequency of S. stercoralis infection in alcoholics. Thus, coproparasitological examination was carried out in 145 subjects, from which 45 were chronic alcoholics (mean age of 45.7 +/- 11.0 years), 10 were nonalcoholic cirrhotic patients (mean age of 50.2 +/- 13.1 years), and 90 were asymptomatic nonalcoholic subjects (mean age of 46.7 +/- 10.1 years), which served as controls. From the alcoholics, 9 had hepatic cirrhosis, 9 had chronic pancreatitis and 27 had neither cirrhosis nor pancreatitis. For the diagnosis of strongyloidiasis, the Baermann-Moraes and Lutz methods were used in three fecal samples from each subject. Samples were collected at alternated days, and three slides of each sample were analyzed for each method, thus totalizing 2,610 slides examined. The frequency of strongloidiasis in the total alcoholic group (33.3%) and in the subgroups of alcoholics, i.e., patients with hepatic cirrhosis (44.4%), with chronic pancreatitis (33.3%), and those with no cirrhosis or pancreatitis (29.6%) was statistically higher than that found in the control group (5.5%). None of the individuals with nonalcoholic hepatic cirrhosis had S. stercoralis infection. Our results showed that the chronic alcoholism itself is an important factor that predisposes to strongyloidiasis. 相似文献
59.
Motta TR Moreira-Filho CA Mendes RP Souza LR Sugizak MF Baueb S Calich VL Vaz CA 《FEMS immunology and medical microbiology》2002,33(3):151-157
Randomly amplified polymorphic DNA (RAPD) analysis of 35 Paracoccidioides brasiliensis isolates was carried out to evaluate the correlation of RAPD profiles with the virulence degree or the type of the clinical manifestations of human paracoccidioidomycosis. The dendrogram presented two main groups sharing 64% genetic similarity. Group A included two isolates from patients with chronic paracoccidioidomycosis; group B comprised the following isolates showing 65% similarity: two non-virulent, six attenuated, five virulent, eight from patients with chronic paracoccidioidomycosis and two from patients with acute paracoccidioidomycosis. The virulent Pb18 isolate and six attenuated or non-virulent samples derived from it were genetically indistinguishable (100% of similarity). Thus, in our study, RAPD patterns could not discriminate among 35 P. brasiliensis isolates according to their differences either in the degree of virulence or in the type of the clinical manifestation of this fungal infection. 相似文献
60.
The progress achieved by several groups in the field of computational protein design shows that successful design methods include two major features: efficient algorithms to deal with the combinatorial exploration of sequence space and optimal energy functions to rank sequences according to their fitness for the given fold. 相似文献