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251.
252.
Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF 总被引:3,自引:0,他引:3
R E Donahue E A Wang D K Stone R Kamen G G Wong P K Sehgal D G Nathan S C Clark 《Nature》1986,321(6073):872-875
Certain proteins are known to play an important part in the proliferation, differentiation and functional activation of haematopoietic progenitor cells in vitro. These proteins include erythropoietin and various colony-stimulating factors (CSFs), one of which is granulocyte-macrophage colony-stimulating factor (GM-CSF). Recently, both murine and human GM-CSF have been purified to homogeneity and complementary DNAs encoding them have been cloned. Although the in vitro activity of recombinant human GM-CSF has been investigated intensively, little is known about the functional activity of this protein in vivo. There is strong evidence that colony-stimulating activities produced by various human and murine tumour tissues and cell lines can stimulate granulopoiesis in mice, as can human urinary extracts. A partially purified preparation of human urinary colony-stimulating factor, however, proved only marginally effective in stimulating granulopoiesis in humans. All these studies suffer from the lack of a homogeneous preparation of colony-stimulating factor. It has recently been shown that recombinant murine multi-CSF or interleukin-3 can stimulate haematopoiesis in mice in vivo. Large-scale production of recombinant human GM-CSF now permits us to examine its effects in vivo using a primate model. We find that the continuous infusion of GM-CSF in healthy monkeys rapidly elicits a dramatic leukocytosis and a substantial reticulocytosis. A similar effect has been observed in one pancytopenic, immunodeficient rhesus macaque. These results suggest that GM-CSF could prove useful in several clinical situations. 相似文献
253.
A total of 66 algal species representing 32 genera were recovered from soils of 10 sites in the Catavi?a region of the Central Desert of Baja California, Mexico. The most common species encountered were the cyanophytes Nostoc commune and Schizothrix calcicola , the chlorophyte Myrmecia astigmatica , and the diatoms Hantzschia amphioxys, Hantzschia amphyoxys f. capitata, Luticola cohnii, Luticola mutica , and Pinnularia borealis var. scalarts . Nine species not found in any previous studies of North American desert soils were present in our study sites, including 3 taxa new to science: Cylindrocystis brebissonii var. deserti , var. nov.; Elakatothrix obtusata , sp. nov.; and Fasciculochloris mexicana , sp. nov. Attempts to correlate species composition with soil chemical and physical parameters were unsuccessful apart from a pH effect on cyanobacterial distribution. Overall composition of the soil algal community in the Catavi?a region is distinct from other desert sites we have studies, although some cosmopolitan desert soil taxa were present. 相似文献
254.
255.
Activation of BPV-1 replication in vitro by the transcription factor E2. 总被引:53,自引:0,他引:53
256.
Lizard cells from the tails of geckos were readily morphologically and antigenically transformed in vitro by SV40 virus. Neither autografts of these cells nor allografts of SV40 transformed gecko embryo cells produced tumors in animals under observation for 1 to 3 years. 相似文献
257.
258.
Clark IE Dodson MW Jiang C Cao JH Huh JR Seol JH Yoo SJ Hay BA Guo M 《Nature》2006,441(7097):1162-1166
Parkinson's disease is the second most common neurodegenerative disorder and is characterized by the degeneration of dopaminergic neurons in the substantia nigra. Mitochondrial dysfunction has been implicated as an important trigger for Parkinson's disease-like pathogenesis because exposure to environmental mitochondrial toxins leads to Parkinson's disease-like pathology. Recently, multiple genes mediating familial forms of Parkinson's disease have been identified, including PTEN-induced kinase 1 (PINK1; PARK6) and parkin (PARK2), which are also associated with sporadic forms of Parkinson's disease. PINK1 encodes a putative serine/threonine kinase with a mitochondrial targeting sequence. So far, no in vivo studies have been reported for pink1 in any model system. Here we show that removal of Drosophila PINK1 homologue (CG4523; hereafter called pink1) function results in male sterility, apoptotic muscle degeneration, defects in mitochondrial morphology and increased sensitivity to multiple stresses including oxidative stress. Pink1 localizes to mitochondria, and mitochondrial cristae are fragmented in pink1 mutants. Expression of human PINK1 in the Drosophila testes restores male fertility and normal mitochondrial morphology in a portion of pink1 mutants, demonstrating functional conservation between human and Drosophila Pink1. Loss of Drosophila parkin shows phenotypes similar to loss of pink1 function. Notably, overexpression of parkin rescues the male sterility and mitochondrial morphology defects of pink1 mutants, whereas double mutants removing both pink1 and parkin function show muscle phenotypes identical to those observed in either mutant alone. These observations suggest that pink1 and parkin function, at least in part, in the same pathway, with pink1 functioning upstream of parkin. The role of the pink1-parkin pathway in regulating mitochondrial function underscores the importance of mitochondrial dysfunction as a central mechanism of Parkinson's disease pathogenesis. 相似文献
259.
Xu X Clark JM Forster CA Norell MA Erickson GM Eberth DA Jia C Zhao Q 《Nature》2006,439(7077):715-718
The tyrannosauroid fossil record is mainly restricted to Cretaceous sediments of Laurasia, although some very fragmentary Jurassic specimens have been referred to this group. Here we report a new basal tyrannosauroid, Guanlong wucaii gen. et sp. nov., from the lower Upper Jurassic of the Junggar Basin, northwestern China. G. wucaii is the oldest known tyrannosauroid and shows several unexpectedly primitive pelvic features. Nevertheless, the limbs of G. wucaii share several features with derived coelurosaurs, and it possesses features shared by other coelurosaurian clades. This unusual combination of character states provides an insight into the poorly known early radiation of the Coelurosauria. Notably, the presumed predatory Guanlong has a large, fragile and highly pneumatic cranial crest that is among the most elaborate known in any non-avian dinosaur and could be comparable to some classical exaggerated ornamental traits among vertebrates. 相似文献
260.
Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2 总被引:10,自引:0,他引:10
Metherell LA Chapple JP Cooray S David A Becker C Rüschendorf F Naville D Begeot M Khoo B Nürnberg P Huebner A Cheetham ME Clark AJ 《Nature genetics》2005,37(2):166-170
Familial glucocorticoid deficiency (FGD), or hereditary unresponsiveness to adrenocorticotropin (ACTH; OMIM 202200), is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex, which stimulates glucocorticoid production. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia or overwhelming infection in infancy or childhood. Mutations of the ACTH receptor (melanocortin 2 receptor, MC2R) account for approximately 25% of cases of FGD. FGD without mutations of MC2R is called FGD type 2. Using SNP array genotyping, we mapped a locus involved in FGD type 2 to chromosome 21q22.1. We identified mutations in a gene encoding a 19-kDa single-transmembrane domain protein, now known as melanocortin 2 receptor accessory protein (MRAP). We show that MRAP interacts with MC2R and may have a role in the trafficking of MC2R from the endoplasmic reticulum to the cell surface. 相似文献