全文获取类型
收费全文 | 1610篇 |
免费 | 108篇 |
专业分类
1718篇 |
出版年
2023年 | 9篇 |
2022年 | 17篇 |
2021年 | 24篇 |
2020年 | 16篇 |
2019年 | 33篇 |
2018年 | 35篇 |
2017年 | 36篇 |
2016年 | 48篇 |
2015年 | 57篇 |
2014年 | 64篇 |
2013年 | 87篇 |
2012年 | 111篇 |
2011年 | 106篇 |
2010年 | 78篇 |
2009年 | 43篇 |
2008年 | 72篇 |
2007年 | 67篇 |
2006年 | 78篇 |
2005年 | 66篇 |
2004年 | 55篇 |
2003年 | 61篇 |
2002年 | 70篇 |
2001年 | 24篇 |
2000年 | 10篇 |
1999年 | 18篇 |
1998年 | 18篇 |
1997年 | 16篇 |
1996年 | 23篇 |
1995年 | 9篇 |
1994年 | 15篇 |
1993年 | 14篇 |
1992年 | 12篇 |
1991年 | 18篇 |
1990年 | 19篇 |
1989年 | 17篇 |
1988年 | 14篇 |
1987年 | 16篇 |
1984年 | 11篇 |
1983年 | 11篇 |
1982年 | 26篇 |
1981年 | 16篇 |
1979年 | 12篇 |
1978年 | 9篇 |
1976年 | 10篇 |
1975年 | 12篇 |
1974年 | 14篇 |
1973年 | 20篇 |
1972年 | 11篇 |
1971年 | 10篇 |
1968年 | 8篇 |
排序方式: 共有1718条查询结果,搜索用时 15 毫秒
81.
Karel Indrak Vaclav Brabec Jarmila Indrakova Ladislav Chrobak Adriana Sakalova Marie Jarosova Jaroslav Cermak You-jun Fei Ferdane Kutlar Yuan-chao Gu Erol Baysal Titus H. J. Huisman 《Human genetics》1992,88(4):399-404
Summary We have identified different -thalassemia mutations in 93 members of 34 families of Czech or Slovakian descent using gene amplification, hybridization with specific 32P-labeled oligonucleotide probes, sequencing of amplified DNA, and gene mapping. The GA mutation at IVS-I-1 was found in 18 families; other Mediterranean mutations were IVS-II-1 (GA), IVS-II-745 (CG), IVS-I-110 (GA), and codon 39 (CT); these were present in 9 additional families. The GT mutation at codon 121, known to cause Heinzbody -thalassemia, was present in 3 families, and the frameshift at codons 82/83 (-G), first described in the Azerbaijanian population, in 2 families. A newly discovered allele was a frameshift at codons 38/39 (-C). One -thalassemia allele was incompletely characterized. We observed in 2 families a TC mutation at position +96 UTR (untranslated region) relative to the termination codon; this mutation likely is a rare polymorphism, -Thalassemia was rare; only one person carried the -3.7 heterozygosity, and one other had a yet to be identified -thalassemia-1, while seven had the anti 3.7 triplication. 相似文献
82.
Karel Weidinger 《Journal of Ornithology》2010,151(3):729-735
Nest predation patterns and processes cannot be understood without studying the behaviour of predators. I videotaped the behaviour
of 22 species of predators at 171 depredated nests of 13 passerine species, in woodland in the Czech Republic. About 32% (60/187)
of all events occurred during the night; mammals accounted for 95% (57/60) and 22% (28/127) of nocturnal and diurnal predation,
respectively. About 67% (57/85) of mammalian predation, but only 3% (3/102) of avian predation, occurred during night. Multiple
predations by the same species were detected in at least 7% (6/82) and 42% (37/88) of nests depredated by mammals and birds,
respectively. Martens Martes martes/foina took nest content mostly all at once; birds (mainly Jay Garrulus glandarius) revisited partially depredated nest during 1–4 consecutive days. Martens stayed at the depredated nest about five times
longer than Jays. Martens spent similar time at nests with eggs and nestling, while Jays stayed about twice longer at nests
with eggs. Mammals consumed eggs always at the nest (23/23), but took nestlings away in at least 48% (31/64) cases. Birds
took the eggs and nestling away in at least 31% (18/58) and 76% (71/94) cases, respectively. Predator visits to active nests
without taking the content, repeated partial predation and revisitation of previously depredated nests suggest an effect of
memory on predator’s foraging behaviour. 相似文献
83.
Christine Breynaert Tom Dresselaers Clémentine Perrier Ingrid Arijs Jonathan Cremer Leentje Van Lommel Kristel Van Steen Marc Ferrante Frans Schuit Séverine Vermeire Paul Rutgeerts Uwe Himmelreich Jan L. Ceuppens Karel Geboes Gert Van Assche 《PloS one》2013,8(7)
Introduction
Chronically relapsing inflammation, tissue remodeling and fibrosis are hallmarks of inflammatory bowel diseases. The aim of this study was to investigate changes in connective tissue in a chronic murine model resulting from repeated cycles of dextran sodium sulphate (DSS) ingestion, to mimic the relapsing nature of the human disease.Materials and Methods
C57BL/6 mice were exposed to DSS in drinking water for 1 week, followed by a recovery phase of 2 weeks. This cycle of exposure was repeated for up to 3 times (9 weeks in total). Colonic inflammation, fibrosis, extracellular matrix proteins and colonic gene expression were studied. In vivo MRI T 2 relaxometry was studied as a potential non-invasive imaging tool to evaluate bowel wall inflammation and fibrosis.Results
Repeated cycles of DSS resulted in a relapsing and remitting disease course, which induced a chronic segmental, transmural colitis after 2 and 3 cycles of DSS with clear induction of fibrosis and remodeling of the muscular layer. Tenascin expression mirrored its expression in Crohn’s colitis. Microarray data identified a gene expression profile different in chronic colitis from that in acute colitis. Additional recovery was associated with upregulation of unique genes, in particular keratins, pointing to activation of molecular pathways for healing and repair. In vivo MRI T2 relaxometry of the colon showed a clear shift towards higher T2 values in the acute stage and a gradual regression of T2 values with increasing cycles of DSS.Conclusions
Repeated cycles of DSS exposure induce fibrosis and connective tissue changes with typical features, as occurring in Crohn’s disease. Colonic gene expression analysis revealed unique expression profiles in chronic colitis compared to acute colitis and after additional recovery, pointing to potential new targets to intervene with the induction of fibrosis. In vivo T2 relaxometry is a promising non-invasive assessment of inflammation and fibrosis. 相似文献84.
Yuri M. Moshkin Cecile M. Doyen Tsung-Wai Kan Gillian E. Chalkley Karen Sap Karel Bezstarosti Jeroen A. Demmers Zeliha Ozgur Wilfred F. J. van Ijcken C. Peter Verrijzer 《PLoS genetics》2013,9(9)
Chromosome duplication and transmission into daughter cells requires the precisely orchestrated binding and release of cohesin. We found that the Drosophila histone chaperone NAP1 is required for cohesin release and sister chromatid resolution during mitosis. Genome-wide surveys revealed that NAP1 and cohesin co-localize at multiple genomic loci. Proteomic and biochemical analysis established that NAP1 associates with the full cohesin complex, but it also forms a separate complex with the cohesin subunit stromalin (SA). NAP1 binding to cohesin is cell-cycle regulated and increases during G2/M phase. This causes the dissociation of protein phosphatase 2A (PP2A) from cohesin, increased phosphorylation of SA and cohesin removal in early mitosis. PP2A depletion led to a loss of centromeric cohesion. The distinct mitotic phenotypes caused by the loss of either PP2A or NAP1, were both rescued by their concomitant depletion. We conclude that the balanced antagonism between NAP1 and PP2A controls cohesin dissociation during mitosis. 相似文献
85.
Glucuronic acid conjugates of bilirubin-IXα in normal bile compared with post-obstructive bile. Transformation of the 1-O-acylglucuronide into 2-, 3-, and 4-O-acylglucuronides 总被引:5,自引:2,他引:5 下载免费PDF全文
Frans Compernolle Gustaaf P. Van Hees Norbert Blanckaert Karel P. M. Heirwegh 《The Biochemical journal》1978,171(1):185-201
Structures have been determined for bilirubin-IXalpha conjugates in freshly collected bile of normal rats, dogs and man and in post-obstructive bile of man and rats. The originally secreted conjugate has been characterized as azopigment (I), i.e. a 1-O-acyl-beta-d-glucopyranuronic acid glycoside. Conversion of the acetylated methyl ester of azopigment (I) into methyl 2,3,4-tri-O-acetyl-1-bromo-1-deoxy-beta-d-glucopyranuronate (V) indicates the pyranose ring structure for the carbohydrate and a C-1 attachment for the bilirubin-IXalpha acyl group. Alternative procedures for deconjugation of azopigment (I) and its derivatives are also described. In post-obstructive bile, the 1-O-acylglucuronide is converted into 2-, 3- and 4-O-acylglucuronides via sequential intramolecular migrations of the bilirubin acyl group. The following approach was utilized. (1) The tetrapyrrole conjugates were cleaved to dipyrrolic aniline and ethyl anthranilate azopigments, and the azopigments were separated as the acids or methyl esters. (2) The isomeric methyl esters were characterized by mass spectral analysis of the acetates and silyl ethers. (3) The free glycosidic function was demonstrated by 1-oxime and 1-methoxime derivative formation. (4) The position of the dipyrrolic O-acyl group was determined for the methyl esters by protecting the free hydroxyl groups of the glucuronic acid moieties as the acetals formed with ethyl vinyl ether and by further conversion of the carbohydrates into partially methylated alditol acetates. These were analysed by using g.l.c.-mass spectrometry. The relevance of the present results with regard to previous reports on disaccharidic conjugates is discussed. Details of procedures for the formation of chemical derivatives for g.l.c. and mass spectrometry have been deposited as Supplementary Publication SUP 50081 (15 pages) at the British Library Lending Division, Boston Spa, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1978), 169, 5. 相似文献
86.
Kees Nieuwenhuijsen Ad J. J. C. Lammers Karel J. de Neef A. Koos Slob 《International journal of primatology》1985,6(1):77-99
Reproductive physiology was studied in female stumptail macaques. Initially the monkeys were housed indoors (individually
and in small groups) and later as one large (92 individuals) social group in an outdoor cage. Most data were collected during
the 4-year outdoor period. Plasma progesterone determination in blood samples taken at weekly intervals allowed estimation
of ovulation and conception dates. The age at first ovulation (X =3.73 years) was positively correlated with body weight at 3 years of age. The average age at first birth was 4.90 years. Gestation
lengths averaged 176.6 days. Following a live birth ovulations returned after a mean interval of 11 months but following an
abortion or still birth this interval was 1 month. Usually a number of ovulatory cycles (X =2.37) preceded a conception. Interbirth intervals (IBIs) in the outdoor cage (X =619.4 days) were significantly longer than IBIs during the indoor period (X =523.1), because indoors the infants were weaned at the age of 7 months, while outdoors weaning occurred more naturally. IBIs
following abortions or still births (X =291.9 days) were significantly shorter than IBIs following live births. Age at first ovulation, age at first birth, IBIs,
and infant production rates were not correlated with dominance rank. Ovarian cycle lengths (X =30.2 days, mode = 28 days) were comparable to previously reported data from laboratory-housed stumptails. No systematic seasonal
fluctuations were found in the onset of sexual maturity, in ovarian cycle lengths, in copulation frequencies, and in distribution
of births. 相似文献
87.
Cyanobacteria are one of the most successful and oldest forms of life that are present on Earth. They are prokaryotic photoautotrophic microorganisms that colonize so diverse environments as soil, seawater, and freshwater, but also stones, plants, or extreme habitats such as snow and ice as well as hot springs. This diversity in the type of environment they live in requires a successful adaptation to completely different conditions. For this reason, cyanobacteria form a wide range of different secondary metabolites. In particular, the cyanobacteria living in both freshwater and sea produce many metabolites that have biological activity. In this review, we focus on metabolites called siderophores, which are low molecular weight chemical compounds specifically binding iron ions. They have a relatively low molecular weight and are produced by bacteria and also by fungi. The main role of siderophores is to obtain iron from the environment and to create a soluble complex available to microbial cells. Siderophores play an important role in microbial ecology; for example, in agriculture they support the growth of many plants and increase their production by increasing the availability of Fe in plants. The aim of this review is to demonstrate the modern use of physico-chemical methods for the detection of siderophores in cyanobacteria and the use of these methods for the detection and characterization of the siderophore-producing microorganisms. Using high-performance liquid chromatography-mass spectrometry (LC-MS), it is possible not only to discover new chemical structures but also to identify potential interactions between microorganisms. Based on tandem mass spectrometry (MS/MS) analyses, previous siderophore knowledge can be used to interpret MS/MS data to examine both known and new siderophores. 相似文献
88.
Irfan Jawed Margarita Velarde Roland Därr Katherine I. Wolf Karen Adams Aradhana M. Venkatesan Sanjeeve Balasubramaniam Marianne S. Poruchynsky James C. Reynolds Karel Pacak Tito Fojo 《Cellular and molecular neurobiology》2018,38(5):1099-1106
Patients harboring germline mutations in the succinate dehydrogenase complex subunit B (SDHB) gene present with pheochromocytomas and paragangliomas (PPGL) that are more likely malignant and clinically aggressive. The combination chemotherapy cyclophosphamide, vincristine, and dacarbazine (CVD) was retrospectively evaluated in patients with SDHB-associated metastatic PPGL.Query Twelve metastatic PPGL patients harboring SDHB mutations/polymorphisms with undetectable SDHB immunostaining were treated with CVD. CVD therapy consisted of 750 mg/m2 cyclophosphamide with 1.4 mg/m2 vincristine on day 1 and 600 mg/m2 dacarbazine on days 1 and 2, every 21–28 days. Treatment outcome was determined by RECIST criteria as well as determination of response duration and progression-free and overall survivals. A median of 20.5 cycles (range 4–41) was administered. All patients had tumor reduction (12–100% by RECIST). Complete response was seen in two patients, while partial response was observed in 8. The median number of cycles to response was 5.5. Median duration of response was 478 days, with progression-free and overall survivals of 930 and 1190 days, respectively. Serial [18F]-fluorodeoxyglucose positron emission tomography and computed tomography imaging demonstrated continued incremental reduction in maximal standardized uptake values (SUVmax) values in 26/30 lesions. During treatment administration, the median SUV decreased from?> 25 to?< 6, indicating the efficacy of chemotherapy over a prolonged period of time. Prolonged therapy results in continued incremental tumor reduction, and is consistent with persistent drug sensitivity. CVD chemotherapy is recommended to be considered part of the initial management in patients with metastatic SDHB-related PPGL. 相似文献
89.
Pablo García-Gómez Abdellatif Bahaji Samuel Gámez-Arcas Francisco José Muñoz Ángela María Sánchez-López Goizeder Almagro Edurne Baroja-Fernández Kinia Ameztoy Nuria De Diego Lydia Ugena Lukáš Spíchal Karel Doležal Mohammad-Reza Hajirezaei Luis C. Romero Irene García Javier Pozueta-Romero 《Plant, cell & environment》2020,43(10):2551-2570
90.
Bendlová B Zavadilová J Vanková M Vejrazková D Lukásová P Vcelák J Hill M Cibula D Vondra K Stárka L Vrbíková J 《The Journal of steroid biochemistry and molecular biology》2007,104(1-2):68-74
SHBG (sex hormone-binding globulin) is a transport protein specific for dihydrotestosterone, testosterone and estradiol. The missense mutation in exon 8 (GAC-->AAC) causing the amino acid exchange Asp-->Asn in codon 327 (D327N) correlates according to the published data with increased SHBG levels. We studied possible association of this polymorphism with polycystic ovary syndrome (PCOS) and anthropometric and biochemical parameters in 248 PCOS patients and 109 healthy control women. The D327N polymorphism (wild-type and variant allele) was detected using PCR-RFLP method (restriction enzyme Bbs-I). For statistical evaluation chi(2) test, Mann-Whitney test, ANCOVA, ANOVA (NCSS 2004, Statgraphics Plus v.5.1, USA) were used. There was no significant difference in genotype distribution between PCOS and controls (chi(2)=1.03, p=0.59). Moreover, we did not find an association of the variant allele with plasma SHBG level, steroid hormones, or screened parameters of lipid and glucose metabolism. In conclusion, the D327N polymorphism of the SHBG gene does not influence susceptibility to PCOS. 相似文献