全文获取类型
收费全文 | 3293篇 |
免费 | 194篇 |
专业分类
3487篇 |
出版年
2024年 | 2篇 |
2023年 | 19篇 |
2022年 | 43篇 |
2021年 | 94篇 |
2020年 | 42篇 |
2019年 | 75篇 |
2018年 | 110篇 |
2017年 | 116篇 |
2016年 | 166篇 |
2015年 | 170篇 |
2014年 | 222篇 |
2013年 | 245篇 |
2012年 | 294篇 |
2011年 | 306篇 |
2010年 | 199篇 |
2009年 | 115篇 |
2008年 | 223篇 |
2007年 | 191篇 |
2006年 | 157篇 |
2005年 | 181篇 |
2004年 | 117篇 |
2003年 | 128篇 |
2002年 | 85篇 |
2001年 | 15篇 |
2000年 | 11篇 |
1999年 | 16篇 |
1998年 | 17篇 |
1997年 | 15篇 |
1996年 | 5篇 |
1995年 | 14篇 |
1994年 | 12篇 |
1993年 | 11篇 |
1992年 | 12篇 |
1991年 | 8篇 |
1990年 | 3篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1985年 | 3篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1967年 | 1篇 |
1957年 | 1篇 |
1955年 | 1篇 |
1954年 | 2篇 |
1948年 | 1篇 |
1945年 | 1篇 |
排序方式: 共有3487条查询结果,搜索用时 0 毫秒
91.
Magdalena T. Tosteson Michael P. Caulfield Jay J. Levy Michael Rosenblatt Daniel C. Tosteson 《Bioscience reports》1988,8(2):173-183
We have used the chemically synthesized sequence of pre-pro-parathyroid hormone and several of its analogues to test the notion that the capacity of amphipathic peptides to aggregate in membranes and form ion-permeable channels correlates with their ability to function as signal sequences for secreted proteins. We found that pre-pro-parathyroid hormone (the signal sequence and pro-region of parathyroid hormone (M)), as well as some of its analogues, forms aggregates of monomers which are ion-permeable. The ion-permeable aggregates (2–3 monomers) formed by (M) are voltage-dependent and are more permeable for cations than for anions. The compounds which formed ion channels in bilayers also acted as potential signal sequences. We conclude that the ability of peptides to form ion-permeable pathways in bilayers may be correlated to their ability to function as signal peptides. 相似文献
92.
Blood parasites shape extreme major histocompatibility complex diversity in a migratory passerine 下载免费PDF全文
Aleksandra Biedrzycka Wojciech Bielański Adam Ćmiel Wojciech Solarz Tadeusz Zając Magdalena Migalska Alvaro Sebastian Helena Westerdahl Jacek Radwan 《Molecular ecology》2018,27(11):2594-2603
Pathogens are one of the main forces driving the evolution and maintenance of the highly polymorphic genes of the vertebrate major histocompatibility complex (MHC). Although MHC proteins are crucial in pathogen recognition, it is still poorly understood how pathogen‐mediated selection promotes and maintains MHC diversity, and especially so in host species with highly duplicated MHC genes. Sedge warblers (Acrocephalus schoenobaenus) have highly duplicated MHC genes, and using data from high‐throughput MHC genotyping, we were able to investigate to what extent avian malaria parasites explain temporal MHC class I supertype fluctuations in a long‐term study population. We investigated infection status and infection intensities of two different strains of Haemoproteus, that is avian malaria parasites that are known to have significant fitness consequences in sedge warblers. We found that prevalence of avian malaria in carriers of specific MHC class I supertypes was a significant predictor of their frequency changes between years. This finding suggests that avian malaria infections partly drive the temporal fluctuations of the MHC class I supertypes. Furthermore, we found that individuals with a large number of different supertypes had higher resistance to avian malaria, but there was no evidence for an optimal MHC class I diversity. Thus, the two studied malaria parasite strains appear to select for a high MHC class I supertype diversity. Such selection may explain the maintenance of the extremely high number of MHC class I gene copies in sedge warblers and possibly also in other passerines where avian malaria is a common disease. 相似文献
93.
Magdalena Wąsik Katarzyna Nazimek Krzysztof Bryniarski 《Microbiology and immunology》2018,62(8):485-496
94.
Magdalena Polak-Berecka Adam Waśko Roman Paduch Tomasz Skrzypek Anna Sroka-Bartnicka 《Antonie van Leeuwenhoek》2014,106(4):751-762
The aim of this study was to analyze the cell envelope components and surface properties of two phenotypes of Lactobacillus rhamnosus isolated from the human gastrointestinal tract. The ability of the bacteria to adhere to human intestinal cells and to aggregate with other bacteria was determined. L. rhamnosus strains E/N and PEN differed with regard to the presence of exopolysaccharides (EPS) and specific surface proteins. Transmission electron microscopy showed differences in the structure of the outer cell surface of the strains tested. Bacterial surface properties were analyzed by Fourier transform infrared spectroscopy, fatty acid methyl esters and hydrophobicity assays. Aggregation capacity and adhesion of the tested strains to the human colon adenocarcinoma cell line HT29 was determined. The results indicated a high adhesion and aggregation ability of L. rhamnosus PEN, which possessed specific surface proteins, had a unique fatty acid content, and did not synthesize EPS. Adherence of L. rhamnosus was dependent on specific interactions and was promoted by surface proteins (42–114 kDa) and specific fatty acids. Polysaccharides likely hindered bacterial adhesion and aggregation by masking protein receptors. This study provides information on the cell envelope constituents of lactobacilli that influence bacterial aggregation and adhesion to intestinal cells. This knowledge will help to understand better their specific contribution in commensal–host interactions and adaptation to this ecological niche. 相似文献
95.
Ewa Maciaszczyk-Dziubinska Magdalena MigockaDonata Wawrzycka Katarzyna MarkowskaRobert Wysocki 《生物化学与生物物理学报:生物膜》2014
The yeast transporter Acr3p is a low affinity As(III)/H+ and Sb(III)/H+ antiporter located in the plasma membrane. It has been shown for bacterial Acr3 proteins that just a single cysteine residue, which is located in the middle of the fourth transmembrane region and conserved in all members of the Acr3 family, is essential for As(III) transport activity. Here, we report a systematic mutational analysis of all nine cysteine residues present in the Saccharomyces cerevisiae Acr3p. We found that mutagenesis of highly conserved Cys151 resulted in a complete loss of metalloid transport function. In addition, lack of Cys90 and Cys169, which are conserved in eukaryotic members of Acr3 family, impaired Acr3p trafficking to the plasma membrane and greatly reduced As(III) efflux, respectively. Mutagenesis of five other cysteines in Acr3p resulted in moderate reduction of As(III) transport capacities and sorting perturbations. Our data suggest that interaction of As(III) with multiple thiol groups in the yeast Acr3p may facilitate As(III) translocation across the plasma membrane. 相似文献
96.
Liliana Surmacz Danuta Plochocka Magdalena Kania Witold Danikiewicz Ewa Swiezewska 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2014,1841(2):240-250
cis-Prenyltransferases (CPTs) comprise numerous enzymes synthesizing isoprenoid hydrocarbon skeleton with isoprenoid units in the cis (Z) configuration. The chain-length specificity of a particular plant CPT is in most cases unknown despite the composition of the accumulated isoprenoids in the tissue of interest being well established. In this report AtCPT6, one of the nine Arabidopsis thaliana CPTs, is shown to catalyze the synthesis of a family of very short-chain polyisoprenoid alcohols of six, seven, and eight isoprenoid units, those of seven units dominating. The product specificity of AtCPT6 was established in vivo following its expression in the heterologous system of the yeast Saccharomyces cerevisiae and was confirmed by the absence of specific products in AtCPT6 T-DNA insertion mutants and their overaccumulation in AtCPT6-overexpressing plants. These observations are additionally validated in silico using an AtCPT6 model obtained by homology modeling. AtCPT6 only partially complements the function of the yeast homologue of CPT-Rer2 since it restores the growth but not protein glycosylation in rer2Δ yeast. This is the first in planta characterization of specific products of a plant CPT producing polyisoprenoids. Their distribution suggests that a joint activity of several CPTs is required to produce the complex mixture of polyisoprenoid alcohols found in Arabidopsis roots. 相似文献
97.
Holger Kneuper Zhen Ping Cao Kate B. Twomey Martin Zoltner Franziska Jäger James S. Cargill James Chalmers Magdalena M. van der Kooi‐Pol Jan Maarten van Dijl Robert P. Ryan William N. Hunter Tracy Palmer 《Molecular microbiology》2014,93(5):928-943
The Type VII protein secretion system, found in Gram‐positive bacteria, secretes small proteins, containing a conserved W‐x‐G amino acid sequence motif, to the growth medium. Staphylococcus aureus has a conserved Type VII secretion system, termed Ess, which is dispensable for laboratory growth but required for virulence. In this study we show that there are unexpected differences in the organization of the ess gene cluster between closely related strains of S. aureus. We further show that in laboratory growth medium different strains of S. aureus secrete the EsxA and EsxC substrate proteins at different growth points, and that the Ess system in strain Newman is inactive under these conditions. Systematic deletion analysis in S. aureus RN6390 is consistent with the EsaA, EsaB, EssA, EssB, EssC and EsxA proteins comprising core components of the secretion machinery in this strain. Finally we demonstrate that the Ess secretion machinery of two S. aureus strains, RN6390 and COL, is important for nasal colonization and virulence in the murine lung pneumonia model. Surprisingly, however, the secretion system plays no role in the virulence of strain SA113 under the same conditions. 相似文献
98.
Palynological records from the annually laminated sediments of Lake Gosciaz are presented for the period ca. 7600–3900 conventional B.P. Indications in percentage and influx diagrams of Mesolithic and Early Neolithic human impact on the natural environment around the lake are discussed and compared with the archaeological evidence. The first indications of human disturbance start at ca. 6700 B.P. and in the following period four disturbance phases with interruptions are distinguished. A relationship between the Elm Decline and an increasing thickness of annual sediment layers as a consequence of increased soil erosion is suggested. Some hitherto unrecognized or incompletely known microfossils are identified and figured, and their palaeoecological significance is discussed. The records of akinetes of Aphanizomenon probably indicate increasing eutrophication of the lake. Charred fragments of grass epidermis are possibly indicative of openings in the forest. 相似文献
99.
100.
Magdalena Marcińska Ewelina Po?piech Sarah Abidi Jeppe Dyrberg Andersen Margreet van den Berge ángel Carracedo Mayra Eduardoff Anna Marczakiewicz-Lustig Niels Morling Titia Sijen Ma?gorzata Skowron Jens S?chtig Denise Syndercombe-Court Natalie Weiler The EUROFORGEN-NoE Consortium Peter M. Schneider David Ballard Claus B?rsting Walther Parson Chris Phillips Wojciech Branicki 《PloS one》2015,10(5)
Androgenetic alopecia, known in men as male pattern baldness (MPB), is a very conspicuous condition that is particularly frequent among European men and thus contributes markedly to variation in physical appearance traits amongst Europeans. Recent studies have revealed multiple genes and polymorphisms to be associated with susceptibility to MPB. In this study, 50 candidate SNPs for androgenetic alopecia were analyzed in order to verify their potential to predict MPB. Significant associations were confirmed for 29 SNPs from chromosomes X, 1, 5, 7, 18 and 20. A simple 5-SNP prediction model and an extended 20-SNP model were developed based on a discovery panel of 305 males from various European populations fitting one of two distinct phenotype categories. The first category consisted of men below 50 years of age with significant baldness and the second; men aged 50 years or older lacking baldness. The simple model comprised the five best predictors: rs5919324 near AR, rs1998076 in the 20p11 region, rs929626 in EBF1, rs12565727 in TARDBP and rs756853 in HDAC9. The extended prediction model added 15 SNPs from five genomic regions that improved overall prevalence-adjusted predictive accuracy measured by area under the receiver characteristic operating curve (AUC). Both models were evaluated for predictive accuracy using a test set of 300 males reflecting the general European population. Applying a 65% probability threshold, high prediction sensitivity of 87.1% but low specificity of 42.4% was obtained in men aged <50 years. In men aged ≥50, prediction sensitivity was slightly lower at 67.7% while specificity reached 90%. Overall, the AUC=0.761 calculated for men at or above 50 years of age indicates these SNPs offer considerable potential for the application of genetic tests to predict MPB patterns, adding a highly informative predictive system to the emerging field of forensic analysis of externally visible characteristics. 相似文献