全文获取类型
收费全文 | 542篇 |
免费 | 79篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 11篇 |
2018年 | 13篇 |
2017年 | 22篇 |
2016年 | 19篇 |
2015年 | 21篇 |
2014年 | 34篇 |
2013年 | 41篇 |
2012年 | 44篇 |
2011年 | 48篇 |
2010年 | 24篇 |
2009年 | 24篇 |
2008年 | 31篇 |
2007年 | 25篇 |
2006年 | 19篇 |
2005年 | 26篇 |
2004年 | 29篇 |
2003年 | 25篇 |
2002年 | 14篇 |
2001年 | 9篇 |
2000年 | 10篇 |
1999年 | 5篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 6篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1992年 | 6篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 4篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1973年 | 3篇 |
1971年 | 3篇 |
1970年 | 4篇 |
1968年 | 2篇 |
1966年 | 2篇 |
1963年 | 1篇 |
排序方式: 共有621条查询结果,搜索用时 31 毫秒
41.
Gauchel G Huppertz B Feiertag H Keller R 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,787(2):271-279
Adulteration of samples is a serious problem in the analysis of drugs of abuse. One of the most frequent methods is substitution of urines by "clean" urines to gain false-negative results in laboratory tests for drugs of abuse. One way to approach this problem may be to label the patient's urine with marker substances which are given orally prior to the delivery of urine. This concept is based on methods for determining malabsorption in pediatric medicine. We report a protocol for evaluating low-molecular-mass polyethylene glycols as enteral labelling marker substances. For monitoring renal excretion of the ingested polyethylene glycols we have developed and optimised an isocratic reversed-phase high-performance liquid chromatographic method with automatic sample cleanup by column switching in the back-flush technique and with RI detection. The chromatographic procedure is simple, reliable and rapid, allowing a high sample throughput for routine screening. 相似文献
42.
Nield J Kruse O Ruprecht J da Fonseca P Büchel C Barber J 《The Journal of biological chemistry》2000,275(36):27940-27946
Electron microscopy and single-particle analyses have been carried out on negatively stained photosystem II (PSII) complexes isolated from the green alga Chlamydomonas reinhardtii and the thermophilic cyanobacterium Synechococcus elongatus. The analyses have yielded three-dimensional structures at 30-A resolution. Biochemical analysis of the C. reinhardtii particle suggested it to be very similar to the light-harvesting complex II (LHCII).PSII supercomplex of spinach, a conclusion borne out by its three-dimensional structure. Not only was the C. reinhardtii LHCII.PSII supercomplex dimeric and of comparable size and shape to that of spinach, but the structural features for the extrinsic OEC subunits bound to the lumenal surface were also similar thus allowing identification of the PsbO, PsbP, and PsbQ OEC proteins. The particle isolated from S. elongatus was also dimeric and retained its OEC proteins, PsbO, PsbU, and PsbV (cytochrome c(550)), which were again visualized as protrusions on the lumenal surface of the complex. The overall size and shape of the cyanobacterial particle was similar to that of a PSII dimeric core complex isolated from spinach for which higher resolution structural data are known from electron crystallography. By building the higher resolution structural model into the projection maps it has been possible to relate the positioning of the OEC proteins of C. reinhardtii and S. elongatus with the underlying transmembrane helices of other major intrinsic subunits of the core complex, D1, D2, CP47, and CP43 proteins. It is concluded that the PsbO protein is located over the CP47 and D2 side of the reaction center core complex, whereas the PsbP/PsbQ and PsbV/PsbU are positioned over the lumenal surface of the N-terminal region of the D1 protein. However, the mass attributed to PsbV/PsbU seems to bridge across to the PsbO, whereas the PsbP/PsbQ proteins protrude out more from the lumenal surface. Nevertheless, within the resolution and quality of the data, the relative positions of the center of masses for OEC proteins of C. reinhardtii and S. elongatus are similar and consistent with those determined previously for the OEC proteins of spinach. 相似文献
43.
Bernd Haditsch Andreas Roessler Peter Krisper Herwig Frisch Helmut G. Hinghofer-Szalkay Nandu Goswami 《PloS one》2015,10(3)
Aims
We investigated changes in volume regulating hormones and renal function at high altitudes and across gender.Methodology
Included in this study were 28 subjects (n = 20 males; n = 8 females. ages: 19 – 65 yrs), who ascended to a height of 3440m (HA1), on the 3rd day and to 5050m (HA2), on the 14th day. Plasma and urinary creatinine and urinary osmolality as well as plasma levels of plasma renin activity (PRA), Aldosterone, antidiuretic hormone (ADH), and atrial natriuretic peptide (ANP) were measured. The plasma volume loss (PVL) was estimated from plasma density and hematocrit. Glomerular filtration rate (GFR) was measured based on nocturnal (9 hour) creatinine clearance; this was compared with various methods for estimation of GFR.Results
The mean 24-hour urine production increased significantly in both sexes across the expedition. But PVL reached significance only in males. No changes in Na+ in plasma, urine or its fractional excretion were seen at both altitudes. Urinary osmolality decreased upon ascent to the higher altitudes. ADH and PRA decreased significantly at both altitudes in males but only at HA2 in females. However, no changes in aldosterone were seen across the sexes and at different altitudes. ANP increased significantly only in males during the expedition. GFR, derived from 9-h creatinine clearance (CreaCl), decreased in both sexes at HA1 but remained stable at HA2. Conventional Crea[p]-based GFR estimates (eGFR) showed only poor correlation to CreaCl.Conclusions
We report details of changes in hormonal patterns across high altitude sojourn. To our knowledge we are not aware of any study that has examined these hormones in same subjects and across gender during high altitude sojourn. Our results also suggest that depending on the estimation formula used, eGFR underestimated the observed decrease in renal function measured by CreaCl, thus opening the debate regarding the use of estimated glomerular filtration rates at high altitudes. 相似文献44.
Hannah M��ller David Schmidt Sandra Steinbrink Ekaterina Mirgorodskaya Verena Lehmann Karin Habermann Felix Dreher Niklas Gustavsson Thomas Kessler Hans Lehrach Ralf Herwig Johan Gobom Aspasia Ploubidou Michael Boutros Bodo M H Lange 《The EMBO journal》2010,29(19):3344-3357
Regulation of centrosome structure, duplication and segregation is integrated into cellular pathways that control cell cycle progression and growth. As part of these pathways, numerous proteins with well‐established non‐centrosomal localization and function associate with the centrosome to fulfill regulatory functions. In turn, classical centrosomal components take up functional and structural roles as part of other cellular organelles and compartments. Thus, although a comprehensive inventory of centrosome components is missing, emerging evidence indicates that its molecular composition reflects the complexity of its functions. We analysed the Drosophila embryonic centrosomal proteome using immunoisolation in combination with mass spectrometry. The 251 identified components were functionally characterized by RNA interference. Among those, a core group of 11 proteins was critical for centrosome structure maintenance. Depletion of any of these proteins in Drosophila SL2 cells resulted in centrosome disintegration, revealing a molecular dependency of centrosome structure on components of the protein translation machinery, actin‐ and RNA‐binding proteins. In total, we assigned novel centrosome‐related functions to 24 proteins and confirmed 13 of these in human cells. 相似文献
45.
Julian Weghuber Anna M. Lipp Jacqueline Stadlbauer Michael C. Aichinger Verena Ruprecht Alois Sonnleitner Gerhard J. Schütz Tamás Henics 《Cell biology international》2010,34(11):1109-1112
The cationic antimicrobial immunomodulatory peptide, KLK (KLKL5KLK), exerts profound membrane interacting properties, impacting on ultrastructure and fluidity. KLK–membrane interactions that lead to these alterations require the ability of the peptide to move into an α‐helical conformation. We show that KLK induces an increase of the intracellular Ca2+ concentration in human T24 cells. The effect of KLK is buffer‐sensitive, as it is detected when HBSS buffer is used, but not with PBS. This, together with the lack of effect of the middle leucine‐to‐proline‐substituted peptide derivative [KPK (KLKLLPLLKLK)], indicates that it is the conformational propensity rather than the net positive charge that contributes to the effect of KLK on intracellular Ca2+ level of T24 cells. We show that, although KLK slightly stimulates Ca2+ influx into the cell, the bulk increase of Ca2+ levels is due to KLK‐induced depletion of intracellular Ca2+ stores. Finally, we demonstrate a KLK‐induced switch of PS (phosphatidylserine) from the inner to the outer plasma membrane leaflet that contributes to the onset of early apoptotic changes in these cells. 相似文献
46.
In order to test if DQB is a good candidate marker to investigate the relationship between major histocompatibility complex
genes and pathogens in natural populations of Mastomys natalensis, we assessed the polymorphism and evolutionary history of this gene. Twenty-four individuals were genotyped for exon 2 of
DQB using capillary electrophoresis single-strand conformation polymorphism, cloning, and sequencing. We found 21 different
alleles. Four individuals show three alleles implying a duplication event in the history of this gene. Each distinct sequence
translates to give a distinct amino acid sequence and there are strong signals of positive selection on peptide binding sites.
Signals of recombination were found in the sequences suggesting that recombination has played a role in generating allelic
diversity. Although trans-taxon polymorphism is present at the interspecific level in DQB exon 2 sequences of Mus species, we did not find any evidence of allele sharing among Muridae genera. This indicates a temporal limit of DQB allele
sharing in Muridae of less than 8 Mya. In conclusion, although DQB seems to be a good marker to investigate pathogen-driven
selection, the polymorphism of gene copy number may restrict its utility in natural populations. 相似文献
47.
The visual pathway is tasked with processing incoming signals from the retina and converting this information into adaptive
behavior. Recent studies of the larval zebrafish tectum have begun to clarify how the 'micro-circuitry' of this highly organized
midbrain structure filters visual input, which arrives in the superficial layers and directs motor output through efferent
projections from its deep layers. The new emphasis has been on the specific function of neuronal cell types, which can now
be reproducibly labeled, imaged and manipulated using genetic and optical techniques. Here, we discuss recent advances and
emerging experimental approaches for studying tectal circuits as models for visual processing and sensorimotor transformation
by the vertebrate brain. 相似文献
48.
49.
Sultan M Piccini I Balzereit D Herwig R Saran NG Lehrach H Reeves RH Yaspo ML 《Genome biology》2007,8(5):R91
Background
Down's syndrome (DS), or trisomy 21, is a complex developmental disorder that exhibits many clinical signs that vary in occurrence and severity among patients. The molecular mechanisms responsible for DS have thus far remained elusive. We argue here that normal variation in gene expression in the population contributes to the heterogeneous clinical picture of DS, and we estimated the amplitude of this variation in 50 mouse orthologs of chromosome 21 genes in brain regions of Ts65Dn (a mouse model of DS). We analyzed the RNAs of eight Ts65Dn and eight euploid mice by real-time polymerase chain reaction. 相似文献50.