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61.
62.
Characteristics of ion and fluid secretion were investigated in isolated Malpighian tubules of the New Zealand Alpine Weta (Hemideina maori). Fluid secretion by tubules in iso-osmotic saline (500mOsm) occurred at a rate of 15+/-3nlh(-1) and was enriched in K(+) (approx. 125mmoll(-1)) relative to the saline (10mmoll(-1)). Maximal fluid secretion (112nlh(-1)) during simultaneous exposure to hypo-osmolality and dibutyryl cAMP resulted in an 8.8x increase in the quantity of K(+) secreted, compared to only a 2.4x increase in Na(+) secretion. Measurements of intracellular ion activities and membrane potentials indicated that Na(+) and K(+) were transported against a strong electrochemical gradient across the apical surface, regardless of saline osmolality. On the basolateral surface, there was a large driving force for Na(+) entry, while K(+) was distributed near its equilibrium potential. Neither bumetanide nor ouabain in the bathing saline had a significant effect on fluid secretion, but Ba(2+) and amiloride decreased fluid secretion by 79 and 57%, respectively. The effect of Ba(2+) on fluid secretion was consistent with a high basolateral permeability to K(+), relative to Na(+) and Cl(-). These results indicate that the characteristics of fluid secretion in this primitive insect are largely conserved with characteristics reported for other insects. 相似文献
63.
Localization of the Gene for Thiamine-Responsive Megaloblastic Anemia Syndrome, on the Long Arm of Chromosome 1, by Homozygosity Mapping 总被引:5,自引:0,他引:5
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Ellis J. Neufeld Hanna Mandel Tal Raz Raymonde Szargel Chandri N. Yandava Amy Stagg Sabine Fauré Timothy Barrett Neil Buist Nadine Cohen 《American journal of human genetics》1997,61(6):1335-1341
Thiamine-responsive megaloblastic anemia, also known as "TRMA" or "Rogers syndrome," is an early-onset autosomal recessive disorder defined by the occurrence of megaloblastic anemia, diabetes mellitus, and sensorineural deafness, responding in varying degrees to thiamine treatment. On the basis of a linkage analysis of affected families of Alaskan and of Italian origin, we found, using homozygosity mapping, that the TRMA-syndrome gene maps to a region on chromosome 1q23.2-23.3 (maximum LOD score of 3.7 for D1S1679). By use of additional consanguineous kindreds of Israeli-Arab origin, the putative disease-gene interval also has been confirmed and narrowed, suggesting genetic homogeneity. Linkage analysis generated the highest combined LOD-score value, 8.1 at a recombination fraction of 0, with marker D1S2799. Haplotype analysis and recombination events narrowed the TRMA locus to a 16-cM region between markers D1S194 and D1S2786. Several heterozygote parents had diabetes mellitus, deafness, or megaloblastic anemia, which raised the possibility that mutations at this locus predispose carriers in general to these manifestations. Characterization of the metabolic defect of TRMA may shed light on the role of thiamine deficiency in such common diseases. 相似文献
64.
Induction of aquaporin-1 mRNA following cardiopulmonary bypass and reperfusion. 总被引:2,自引:0,他引:2
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S. Tabbutt D. P. Nelson N. Tsai T. Miura P. R. Hickey J. E. Mayer E. J. Neufeld 《Molecular medicine (Cambridge, Mass.)》1997,3(9):600-609
BACKGROUND: Cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA) are important components of congenital cardiac surgery. Ischemia/reperfusion injury and inflammatory cascade activation result in endothelial damage and vascular leak which are clinically manifested as pulmonary edema and low cardiac output postoperatively. Newborns are particularly susceptible. Subtraction cloning is a useful method of isolating induced genes and can be applied to CPB/HCA. MATERIALS AND METHODS: We used a newborn lamb model replicating infant CPB with HCA to obtain tissues during various periods of reperfusion. We utilized subtraction cloning to identify mRNA induced in lung following CPB/HCA and reperfusion. Ribonuclease protection was used to quantify mRNA levels. RESULTS: We isolated a cDNA encoding ovine aquaporin-1 in a subtracted cDNA screen comparing control lung with lung exposed to CPB/HCA and reperfusion. Aquaporin-1 mRNA levels increased 3-fold in lung (p = .006) exposed to CPB/HCA and 6 hr of reperfusion. No induction was observed immediately following bypass or after 3 hr of reperfusion. We found no significant induction of aquaporin-1 mRNA following bypass, arrest, and reperfusion in other tissues surveyed, including ventricle, atrium, skeletal muscle, kidney, brain, and liver. CONCLUSIONS: Our finding that aquaporin-1 mRNA is reproducibly induced in lung following CPB/HCA with 6 hr of reperfusion suggests an important role for the water channel in the setting of pulmonary edema. Induction of Aquaporin-1 is late compared with other inflammatory mediators (ICAM-1, E-selectin, IL-8). Further studies are needed to determine if aquaporin-1 contributes to the disease process or if it is part of the recovery phase. 相似文献
65.
T. Raz Tim Barrett Raymonde Szargel Hanna Mandel Ellis J. Neufeld Kazuto Nosaka Marcos B. Viana N. Cohen 《Human genetics》1998,103(4):455-461
Thiamine-responsive megaloblastic anemia (TRMA, also known as Rogers syndrome, OMIM 249270) is a rare autosomal recessive
disorder characterized by a triad of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Patients respond,
to varying degrees, to treatment with megadoses of thiamine. We have recently shown genetic linkage of the TRMA gene to a
16-centimorgan (cM) region on 1q23.2–1q23.3 based on the analysis of four large, inbred families of Alaskan, Italian, and
Israeli-Arab origin. Here we narrow the TRMA interval down to 4 cM based on genetic recombination, homozygosity mapping, and
linkage disequilibrium (highest LOD score of 12.5 at D1S2799, at a recombination fraction of 0). We provide further evidence that the TRMA gene is located in this region and confirm
the homogeneity of the disease. In this analysis, we genotyped seven additional families of diverse ethnic origin (Pakistani,
Indian, Italian, Brazilian, and Japanese), and analyzed additional markers in two previously reported families showing evidence
of linkage disequilibrium in a large area of their haplotypes. The multi-system manifestations of TRMA suggest that thiamine
has a pivotal role in a multiplicity of physiological processes. Mapping the TRMA gene and understanding the molecular basis
of the disease might, thus, shed light on the role of thiamine in common disorders such as deafness, anemia, and diabetes.
Received: 16 April 1998 / Accepted: 6 July 1998 相似文献
66.
67.
A -glucuronidase deficiency mucopolysaccharidosis: studies in cultured fibroblasts 总被引:17,自引:0,他引:17
Cytochrome P-450 cannot be detected spectrophotometrically in testis mitochondria of untreated rats because of the high cytochrome a3 to Cytochrome P-450 ratio. Injection of human chorionic gonadotrophin (HCG) causes a large increase in mitochondrial cytochrome P-450. After 14 days injection, mitochondrial cytochrome P-450 levels are increased 15- to 30-fold (from 0.007 to 0.134 nmoles/mg protein) over control levels. Levels of cytochrome a + a3 are not altered by this treatment. Mitochondrial cytochrome P-450 can also be demonstrated by injection of HCG into rats which were hypophysectomized 24 days previously. During hypophysectorny the mitochondrial cytochromes c + ci, a + a3 and mitochondrial protein decay with halflives of 14, 16, and 15.5 days, respectively. HCG treatment for 8 days increases mitochondrial cytochrome P-450 (from < 0.003 to 0.24 nmoles/mg protein) without altering the levels of the other mitochondrial cytochromes. The control of cytochrome P-450 levels in the mitochondria by HCG suggests that the level of this key component of cholesterol side-chain cleavage enzyme may be of importance in the regulation of steroidogenesis in the testis. 相似文献
68.
Reduction in the rate of DNA reassociation by sequence divergence 总被引:56,自引:0,他引:56
An estimate is made of the effect of imperfectly complementary sequences on the rate of reassociation of DNA. Rate measurements are reported for the reassociation of deaminated DNA and for the pairing of DNAs from related bacteria. A method is presented for separating the effect of the incubation temperature on the rate from the effect of sequence divergence. After correction to the optimum incubation temperature, the rate of DNA reassociation appears to be reduced by a factor of two for each 10 deg. C reduction in melting temperature due to sequence divergence. For most typical cases this effect is modest. However it can be quite important for measurements of the relation between the DNAs of different species. 相似文献
69.
Inhibition of nitrifiers and methanotrophs from an agricultural humisol by allylsulfide and its implications for environmental studies. 总被引:1,自引:0,他引:1
Allylsulfide, an inhibitor of ammonia monooxygenase, was tested to determine its ability to inhibit nitrification and methane oxidation in pure cultures, in agricultural humisol enrichment cultures, and in humisol slurries. We confirmed that allylsulfide is a differential inhibitor of cultures of nitrifiers and methanotrophs at concentrations of 1 and 200 microM, respectively, which result in 50% inhibition. However, although a nitrifying enrichment culture added to sterilized humisol was inhibited 50% by 4 microM allylsulfide, 500 microM allylsulfide was necessary for 50% inhibition of the endogenous nitrifying activity in nonsterile humisol. We concluded that native nitrifiers were protected, possibly by being in colonial aggregates or sheltered microenvironments. 相似文献
70.
Mutations in the leucine zipper motif and sterol-sensing domain inactivate the Niemann-Pick C1 glycoprotein. 总被引:2,自引:0,他引:2
H Watari E J Blanchette-Mackie N K Dwyer M Watari E B Neufeld S Patel P G Pentchev J F Strauss 《The Journal of biological chemistry》1999,274(31):21861-21866
Niemann-Pick type C (NPC) disease, characterized by accumulation of low density lipoprotein-derived free cholesterol in lysosomes, is caused by mutations in the NPC1 gene. We examined the ability of wild-type NPC1 and NPC1 mutants to correct the NPC sterol trafficking defect and their subcellular localization in CT60 cells. Cells transfected with wild-type NPC1 expressed 170- and 190-kDa proteins. Tunicamycin treatment resulted in a 140-kDa protein, the deduced size of NPC1, suggesting that NPC1 is N-glycosylated. Mutation of all four asparagines in potential N-terminal N-glycosylation sites to glutamines resulted in a 20-kDa reduction of the expressed protein. Proteins with a single N-glycosylation site mutation localized to late endosome/lysosomal compartments, as did wild-type NPC1, and each corrected the cholesterol trafficking defect. However, mutation of all four potential N-glycosylation sites reduced ability to correct the NPC phenotype commensurate with reduced expression of the protein. Mutations in the putative sterol-sensing domain resulted in inactive proteins targeted to lysosomal membranes encircling cholesterol-laden cores. N-terminal leucine zipper motif mutants could not correct the NPC defect, although they accumulated in lysosomal membranes. We conclude that NPC1 is a glycoprotein that must have an intact sterol-sensing domain and leucine zipper motif for cholesterol-mobilizing activity. 相似文献