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1.
Dent's disease, which is a renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is associated with inactivating mutations of the X-linked chloride channel, CLC-5. However, the manner in which a functional loss of CLC-5 leads to such diverse renal abnormalities remains to be defined. In order to elucidate this, we performed studies to determine the segmental expression of CLC-5 in the human kidney and to define its intracellular distribution. We raised and characterized antisera against human CLC-5, and identified by immunoblotting an 83 kDa band corresponding to CLC-5 in human kidney cortex and medulla. Immunohistochemistry revealed CLC-5 expression in the epithelial cells lining the proximal tubules and the thick ascending limbs of Henle's loop, and in intercalated cells of the collecting ducts. Studies of subcellular human kidney fractions established that CLC-5 distribution was associated best with that of Rab4, which is a marker of recycling early endosomes. In addition, confocal microscopy studies using the proximal tubular cell model of opossum kidney cells, which endogenously expressed CLC-5, revealed that CLC-5 co-localized with the albumin-containing endocytic vesicles that form part of the receptor-mediated endocytic pathway. Thus, CLC-5 is expressed at multiple sites in the human nephron and is likely to have a role in the receptor-mediated endocytic pathway. Furthermore, the functional loss of CLC-5 in the proximal tubules and the thick ascending limbs provides an explanation for the occurrences of low molecular weight proteinuria and hypercalciuria, respectively. These results help to elucidate further the patho-physiological basis of the renal tubular defects of Dent's disease.  相似文献   
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The peptidoglycan cortex of endospores of Bacillus species is required for maintenance of spore dehydration and dormancy, and the structure of the cortex may also allow it to function in attainment of spore core dehydration. A significant difference between spore and growing cell peptidoglycan structure is the low degree of peptide cross-linking in cortical peptidoglycan; regulation of the degree of this cross-linking is exerted by D,D-carboxypeptidases. We report here the construction of mutant B. subtilis strains lacking all combinations of two and three of the four apparent D, D-carboxypeptidases encoded within the genome and the analysis of spore phenotypic properties and peptidoglycan structure for these strains. The data indicate that while the dacA and dacC products have no significant role in spore peptidoglycan formation, the dacB and dacF products both function in regulating the degree of cross-linking of spore peptidoglycan. The spore peptidoglycan of a dacB dacF double mutant was very highly cross-linked, and this structural modification resulted in a failure to achieve normal spore core dehydration and a decrease in spore heat resistance. A model for the specific roles of DacB and DacF in spore peptidoglycan synthesis is proposed.  相似文献   
3.
OBJECTIVE: To systematically review the effects of isotonic crystalloids compared with colloids in fluid resuscitation. DATA SOURCES: Computerized bibliographic search of published research and citation review of relevant articles. STUDY SELECTION: All randomized clinical trials of adult patients requiring fluid resuscitation comparing isotonic crystalloids vs. colloids were included. Pulmonary edema, mortality, and length of stay were evaluated. Independent review of 105 articles identified 17 relevant primary studies of 814 patients. Weighted c about article inclusion was high (0.76). DATA EXTRACTION: Data on population, interventions, outcomes, and methodologic quality of the studies were obtained by duplicate independent review with differences resolved by consensus. Weighted ic on the validity assessment was moderate (0.54). DATA SYNTHESIS: No difference was observed overall between crystalloid and colloid resuscitation with respect to mortality and pulmonary edema; however, the power of the aggregated data was insufficient to detect small but potentially clinically important differences. Subgroup analysis suggested a statistically significant difference in mortality in trauma in favor of crystalloid resuscitation (relative risk 0.39, 95% confidence intervals: 0.17 to 0.89). Several methodologic issues are noteworthy regarding the primary studies, including lack of blinding (except in three studies). The type, dose, and duration of fluid administration and outcomes measured were different across these trials. CONCLUSIONS: Overall, there is no apparent difference in pulmonary edema, mortality, or length of stay between isotonic crystalloid and colloid resuscitation. Crystalloid resuscitation is associated with a lower mortality in trauma patients. Methodologic limitations preclude any evidence-based clinical recommendations. Larger well-designed randomized trials are needed to achieve sufficient power to detect potentially small differences in treatment effects if they truly exist.  相似文献   
4.
Bone resorption is initiated by osteoclast attachment to the mineralized matrix, cytoskeletal reorganization, cellular polarization, and the formation of the sealing zone. The present study examines the interaction between PYK2 and p130(Cas) (Crk-associated substrate), suggested to be part of the signaling pathway initiated by osteoclast adhesion. Using murine osteoclast-like cells (OCLs) and their mononuclear precursors (pOCs), generated in a co-culture of bone marrow and osteoblastic MB1.8 cells, we show that: 1) p130(Cas) is tyrosine-phosphorylated upon adhesion of pOCs to vitronectin or ligation of beta3 integrins; 2) p130(Cas) colocalizes with PYK2 and the cytoskeletal proteins F-actin, vinculin, and paxillin in the podosomal-rich ring-like structures of OCLs plated on glass and in the sealing zone in actively resorbing OCLs on bone; 3) p130(Cas) and PYK2 form a stable complex in pOCs, independent of tyrosine phosphorylation of either molecule, and this complex is present in Src (-/-) OCLs, in which neither protein is phosphorylated or associated with the osteoclast adhesion structure; 4) the association of p130(Cas) and PYK2 is mediated by the SH3 domain of p130(Cas) and the C-terminal domain of PYK2. These findings suggest that p130(Cas) and its association with PYK2 may play an important role in the adhesion-dependent signaling that leads to cytoskeletal reorganization and formation of the sealing zone during osteoclast activation.  相似文献   
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KinMutBase (http://www.uta.fi/laitokset/imt/KinMut Base.html) is a registry of mutations in human protein kinases related to disorders. Kinases are essential cellular signalling molecules, in which mutations can lead into diseases including, e.g., immunodeficiencies, cancers and endocrine disorders. The first release of KinMutBase contains information for nine protein tyrosine kinases. There are altogether 170 entries representing 273 families and 403 patients. Mutations appear both in conserved hallmark residues of the kinases as well as in non-homologous sites. The KinMutBase WWW pages provide plenty of information, namely mutation statistics and display, clickable sequences with mutations, restriction enzyme patterns and online submission.  相似文献   
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Retinoid signalling plays an important role in embryonic pattern formation. Excess of retinoic acid during gastrulation results in axial defects in vertebrate embryos, suggesting that retinoids are involved in early anteroposterior patterning. To study retinoid signalling in zebrafish embryos, we developed a novel method to detect endogenous retinoids in situ in embryos, using a fusion protein of the ligand inducible transactivation domain of a retinoic acid receptor and a heterologous DNA binding domain. Using this method, we show that retinoid signalling is localized in zebrafish embryos in the region of the embryonic shield, and towards the end of gastrulation in a posterior dorsal domain. To investigate the relationships between the spatial distribution of retinoid signalling and the regulation of retinoid target genes, we studied the downregulation by retinoic acid of two genes expressed in anterior regions of the embryo, goosecoid and otx1. These experiments show that expression of both genes is strongly downregulated in the anterior neurectoderm of zebrafish embryos treated with retinoic acid, whereas mesendodermal expression is only mildly affected. Interestingly, a significant downregulation of goosecoid expression by retinoic acid was observed only during midgastrulation but not in earlier stages. In agreement with these results, spatial expression of goosecoid and otx1 does not overlap with the region of retinoid signalling in the late gastrula. Our data support the hypothesis that a localized retinoid signal is involved in axial patterning during early development, at least in part through the repression of anterior genes in posterior regions of the embryo. Furthermore, our data suggest that the action of retinoids is spatially as well as temporally regulated in the developing embryo.  相似文献   
9.
介绍了一印度尼西亚纺纱厂使用瑞士立达机械工程公司生产的C60型梳棉机在环锭细纱操作方面运转性能和质量的经验。  相似文献   
10.
DNA-based immunization is a promising new technique for generating antibodies in laboratory animals for diagnostic purposes in biological science. The main advantages are the elimination of time and labor and the technically demanding steps of antigen purification. The DNA sequence of the protein of interest, cloned in a suitable in vivo expression vector that is administered intramuscularly or intradermally, is sufficient to induce an immune response in animals. We report the induction of antibodies to tobacco mosaic virus (TMV) coat protein (CP) as a highly immunogenic structural protein and potato virus Y (PVY) P1 protein (P1) as a nonstructural protein. The appropriate nucleotide sequences were introduced in a mammalian expression vector (pSG5) and injected intramuscularly into New Zealand White rabbits (Oryctolagus cuniculus). By 10 days post-injection (dpi) a specific immune response was detected against TMV-CP, while it took about 5 weeks for a response to PVY P1. In both cases the antibody titers were significantly above the corresponding pre-immune serum, however, they were considerably below the titer of the matching conventionally produced antiserum. To our knowledge, this is the first report of DNA-based immunization in order to generate antibodies to plant viral proteins, but further improvements are necessary to increase antibody titers before this promising new technique can be introduced broadly in plant science for diagnostic purposes.  相似文献   
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