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排序方式: 共有652条查询结果,搜索用时 15 毫秒
31.
Dryja TP Adams SM Grimsby JL McGee TL Hong DH Li T Andréasson S Berson EL 《American journal of human genetics》2001,68(5):1295-1298
We isolated and characterized the entire coding sequence of a human gene encoding a protein that interacts with RPGR, a protein that is absent or mutant in many cases of X-linked retinitis pigmentosa. The newly identified gene, called "RPGRIP1" for RPGR-interacting protein (MIM 605446), is located within 14q11, and it encodes a protein predicted to contain 1,259 amino acids. Previously published work showed that both proteins, RPGR and RPGRIP1, are present in the ciliary structure that connects the inner and outer segments of rod and cone photoreceptors. We surveyed 57 unrelated patients who had Leber congenital amaurosis for mutations in RPGRIP1 and found recessive mutations involving both RPGRIP1 alleles in 3 (6%) patients. The mutations all create premature termination codons and are likely to be null alleles. Patients with RPGRIP1 mutations have a degeneration of both rod and cone photoreceptors, and, early in life, they experience a severe loss of central acuity, which leads to nystagmus. 相似文献
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P3 cap modified Phe*-Ala series BACE inhibitors 总被引:1,自引:0,他引:1
Chen SH Lamar J Guo D Kohn T Yang HC McGee J Timm D Erickson J Yip Y May P McCarthy J 《Bioorganic & medicinal chemistry letters》2004,14(1):245-250
With the aim of reducing molecular weight and adjusting log D value of BACE inhibitors to more favorable range for BBB penetration and better bioavailability, we synthesized and evaluated several series of P3 cap modified BACE inhibitors obtained via replacement of the P3NHBoc moiety as seen in 3 with other polar functional groups such as amino, hydroxyl and fluorine. Several promising inhibitors emerging from this P3 cap SAR study (e.g., 15 and 19) demonstrated good enzyme inhibitory potencies (BACE-1 IC(50) <50 nM) and whole cell activities (IC(50) approximately 1 microM). 相似文献
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G L Mariottini R Leardi A Carli 《Bollettino della Società italiana di biologia sperimentale》2000,76(3-4):13-20
The management of the marine environment and resource exploitation depend on the knowledge of both water conditions and ecological relationships between organisms. In the framework of fishing problems, an adequate food availability is important in order to allow maintaining and growth of fish stocks. The tunny-fishing of Camogli, owing to the coco-fibre texture of its net, can improve the trophic resources allowing the settlement of organisms eaten by fish. The distribution and composition of settled organisms was studied during the campaign 1988 by microscopical methods. The results have been elaborated by using multivariate (PCA) methods. Foraminifers, ciliates, hydroids, nematodes and copepods were the mainly observed groups. Their variations with season and depth and the relationships with caught fish species are presented. The elaboration of data by PCA allowed an easy and complete interpretation of the obtained complex data set showing the existence of a "rope" and of a "depth" effect. 相似文献
37.
Aneuploidy tests by means of in situ hybridization with chromosome-specific DNA probes on interphase nuclei have been carried out on human lymphocytes treated with diethylstilbestrol (DES). A DNA probe specific for chromosome Y (Y97), either radioactive or biotinylated, was used for the assays. Autoradiography or FITC-conjugated antibiotin antibodies were employed to visualize the hybridization sites. A significant increase of hyperdiploid nuclei was obtained with both procedures and a dose-related effect was revealed using the biotinylated probe. The results obtained, while giving further support to the evidence that DES is able to induce aneuploidy in cultured human cells, also indicate that the sensitivity of the assay can be improved by using biotinylated probes coupled with fluorescent antibodies. 相似文献
38.
The development of diabetic cardiomyopathy is a key contributor to heart failure and mortality in obesity and type 2 diabetes (T2D). Current therapeutic interventions for T2D have limited impact on the development of diabetic cardiomyopathy. Clearly, new therapies are urgently needed. A potential therapeutic target is protein kinase D (PKD), which is activated by metabolic insults and implicated in the regulation of cardiac metabolism, contractility and hypertrophy. We therefore hypothesised that PKD inhibition would enhance cardiac function in T2D mice. We first validated the obese and T2D db/db mouse as a model of early stage diabetic cardiomyopathy, which was characterised by both diastolic and systolic dysfunction, without overt alterations in left ventricular morphology. These functional characteristics were also associated with increased PKD2 phosphorylation in the fed state and a gene expression signature characteristic of PKD activation. Acute administration of the PKD inhibitor CID755673 to normal mice reduced both PKD1 and 2 phosphorylation in a time and dose-dependent manner. Chronic CID755673 administration to T2D db/db mice for two weeks reduced expression of the gene expression signature of PKD activation, enhanced indices of both diastolic and systolic left ventricular function and was associated with reduced heart weight. These alterations in cardiac function were independent of changes in glucose homeostasis, insulin action and body composition. These findings suggest that PKD inhibition could be an effective strategy to enhance heart function in obese and diabetic patients and provide an impetus for further mechanistic investigations into the role of PKD in diabetic cardiomyopathy. 相似文献
39.
Erynn A Lucas Stephen J Billington Petteri Carlson David J McGee B Helen Jost 《BMC microbiology》2010,10(1):270
Background
Arcanobacterium haemolyticum is an emerging bacterial pathogen, causing pharyngitis and more invasive infections. This organism expresses an unusual phospholipase D (PLD), which we propose promotes bacterial pathogenesis through its action on host cell membranes. The pld gene is found on a genomic region of reduced %G + C, suggesting recent horizontal acquisition. 相似文献40.
T P Dryja J Rapaport T L McGee T M Nork T L Schwartz 《American journal of human genetics》1993,52(6):1122-1128
In one family with low-penetrance retinoblastoma, a germ-line deletion is shared by affected and unaffected, obligate carriers. The deletion encompasses exon 4 of the retinoblastoma gene and corresponds to a mutant protein without residues 127-166. In a second family, RFLP analysis shows that two distant relatives have independently derived mutations. These families, together with others reported elsewhere, indicate that attributes of alleles at the retinoblastoma locus specify penetrance. 相似文献