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981.
    
Human papillomavirus (HPV) E6 and E7 oncoproteins are attractive targets for T-cell-based immunotherapy of cervical cancer. In this study, we demonstrate that dendritic cells (DCs) pulsed with HPV16 E7 protein are not only recognized in vitro by E7-specific CTLs but also elicit E7-specific CTL responses in vivo, associated with protection against a challenge with syngeneic HPV16-induced tumor cells. Vaccination with soluble E7 protein in incomplete Freund's adjuvant likewise induces E7-specific CTL responses associated with tumor protection. The presence of HPV16 E7-specific CTLs in vivo and the observation that depletion of CD8+ cells completely abolishes tumor protection demonstrate that CTLs are the major effector cells in mediating antitumor activity. The in vivo involvement of DCs in the activation of protective CTLs is suggested by the surface display of E7 peptide-loaded MHC class I molecules on these cells after E7 protein immunization. These data show that HPV16 E7 protein-pulsed DCs, as well as the administration of E7 protein antigen in adjuvant, can effectively stimulate tumor-specific MHC class I-restricted CD8+ T-cell-mediated protective immunity to HPV16-induced cancers.  相似文献   
982.
    
The purpose of this study was to determine the risk factors for hepatitis C virus (HCV) infection among drug abusers in southern Taiwan. This survey included 935 drug abusers from Kaohsiung Narcotic Abstention Institute and Kaohsiung prison. The prevalence of anti-HCV antibody was 29.1% among male drug abusers and 19.4% among female drug abusers. The seroprevalence of anti-HCV antibody was 66.4% among intravenous drug abusers and 14.4% among nonintravenous drug abusers. Intravenous drug use, a history of hepatitis, having tattoos, and age were independently related to HCV seropositivity among drug abusers. The prevalence of anti-HCV antibody concentrations significantly increased (10.8-fold) with intravenous drug abuse and with having tattoos (1.7-fold). These findings suggest that hepatitis C virus is mainly transmitted by the parenteral route among drug abusers in southern Taiwan. Due to the high rate of HCV infection among drug abusers, investigation of high-risk behavior should be routine in this group. To prevent HCV infection, emphasis on the use of sterile needles and aseptic procedures in tattooing is important in Taiwan.  相似文献   
983.
    
Not one post, core, margin, impression material, cement, or final restoration can be used in all clinical situations. This article does not discuss the merits and shortcomings of the numerous restorative concepts and techniques that exist, but rather has concentrated on those that the author believes are valid and applicable today. If one third or more of the anatomic crown remains, or if this is achieved by crown lengthening, a post may not be necessary; however, a crown restoration should definitely be considered. Veterinary dentistry cannot limit those variables that occur daily in clinical practice. Veterinarians must learn to work with these variables and spend less time trying to find the one that applies to all cases. When the basic concepts of how to retain the various restorative components and how to protect remaining tooth structure are understood, the ability to answer numerous questions that arise during the restorative process is facilitated and results in final restorations that are based on sound design principles.  相似文献   
984.
    
The authors describes a new device for external tissue extension (ETE) which will be able to replace or complement tissue expanders. The device consists of many ETE units, each unit consisting of a needle and two friction stoppers counted on a silicone string. Application, optimal tension and final surgical procedure are described. The indications are the same as for tissue expanders, e.g. scars, naevi and previous skin grafts, and also concern the closure of acute fasciotomies. The advantages are numerous: very simple technique, application under local anaesthetics, faster cutaneous profits (5-6 days), inexpensive total treatment, low complication rate.  相似文献   
985.
    
Peroxisome-to-mitochondrion mistargeting of the homodimeric enzyme alanine:glyoxylate aminotransferase 1 (AGT) in the autosomal recessive disease primary hyperoxaluria type 1 (PH1) is associated with the combined presence of a normally occurring Pro(11)Leu polymorphism and a PH1-specific Gly170Arg mutation. The former leads to the formation of a novel NH2-terminal mitochondrial targeting sequence (MTS), which although sufficient to direct the import of in vitro-translated AGT into isolated mitochondria, requires the additional presence of the Gly170Arg mutation to function efficiently in whole cells. The role of this mutation in the mistargeting phenomenon has remained elusive. It does not interfere with the peroxisomal targeting or import of AGT. In the present study, we have investigated the role of the Gly170Arg mutation in AGT mistargeting. In addition, our studies have led us to examine the relationship between the oligomeric status of AGT and the peroxisomal and mitochondrial import processes. The results obtained show that in vitro-translated AGT rapidly forms dimers that do not readily exchange subunits. Although the presence of the Pro(11)Leu or Gly170Arg substitutions alone had no effect on dimerization, their combined presence abolished homodimerization in vitro. However, AGT containing both substitutions was still able to form heterodimers in vitro with either normal AGT or AGT containing either substitution alone. Expression of various combinations of normal and mutant, as well as epitope-tagged and untagged forms of AGT in whole cells showed that normal AGT rapidly dimerizes in the cytosol and is imported into peroxisomes as a dimer. This dimerization prevents mitochondrial import, even when the AGT possesses an MTS generated by the Pro(11)Leu substitution. The additional presence of the Gly170Arg substitution impairs dimerization sufficiently to allow mitochondrial import. Pharmacological inhibition of mitochondrial import allows AGT containing both substitutions to be imported into peroxisomes efficiently, showing that AGT dimerization is not a prerequisite for peroxisomal import.  相似文献   
986.
    
The naturally occurring tetrakisphosphate myo-inositol-1,3,4, 6-tetrakisphosphate [Ins(1,3,4,6)P4] was able to release Ca2+ from the intracellular stores of permeabilized rabbit platelets but was 40-fold less potent than D-myo-inositol-1,4,5-trisphosphate [Ins(1,4,5)P3]. The Ca2+ releasing activity of Ins(1,3,4,6)P4 was rationalized by envisaging two alternative receptor binding orientations in which the vicinal D-1,6-bisphosphate of Ins(1,3,4,6)P4 mimics the D-4,5-bisphosphate in the Ins(1,4,5)P3 binding conformation. This rationalization predicted that Ins(1,4,5)P3 regioisomers [i.e, D-myo-inositol -1,4,6-trisphosphate [D-Ins(1,4,6)P3] and D-myo-inositol-1,3,6 -trisphosphate [D-Ins(1,3,6)P3]] should also possess Ca(2+)-releasing activity. The unambiguous total synthesis of the enatiomers of Ins(1,4,6)P3 [i.e., D-Ins(1,4,6)P3 and D-Ins(3,4,6)P3] and the enatiomers of Ins(1,3,4)P3 [i.e., D-Ins(1,3,6)P3 and D-Ins(1,3,4)P3] allowed an examination of this prediction. D-Ins(1,4,6)P3 released Ca2+ from the intracellular stores of permeabilized platelets and was only 2-3-fold less potent than Ins(1,4,5)P3. D-Ins(1,3,6)P3 [alternative nomenclature, L-Ins(1,3,4)P3] also released Ca2+ but was 12-fold less potent than Ins(1,4,5)P3. Both D-Ins(1,4,6)P3 and D-Ins(1,3,6)P3 displaced specifically bound [3H]Ins(1,4,5)P3 from the Ins(1,4,5)P3 receptor on rat cerebellar membranes. In contrast, however, D-Ins(3,4,6)P3 [alternative nomenclature, L-Ins(1,4,6)P3] and D-Ins(1,3,4)P3 neither possessed Ca(2+)-releasing activity nor displaced [3H]Ins(1,4,5)P3. The ability of D-Ins(1,3,6)P3 to release Ca2+ in permeabilized platelets is in contrast to its apparent lack of Ca(2+)-mobilizing activity previously reported in rat basophilic leukemic cells. The possibility that this is a reflection of the different Ins(1,4,5)P3 receptor subtypes possessed by these two cell types is discussed.  相似文献   
987.
    
The fact that organic material is always present and distributed throughout each renal calculus suggests that it may play a role in stone formation. The organic matrix of calcium oxalate (CaOx) crystals freshly generated in urine in vitro contains urinary prothrombin fragment 1 (UPTF1) as the principal protein. In this initial study, matrix was extracted from 12 renal calculi and evaluated for the presence of UPTF1 using Western blotting. UPTF1 was present in all eight stones whose principal component was CaOx, and in one of two stones which consisted mainly of calcium phosphate (CaP). UPTF1 was absent from the two struvite calculi examined. The relationship between CaP and UPTF1 was explored further. Matrix harvested from CaP crystals freshly generated in urine in vitro was also shown to contain UPTF1 as its principal component. Our inability to detect UPTF1 in one mixed CaOx/CaP stone may be related to our methods of matrix retrieval, while its absence from two struvite stones argues against it being present in the other stones merely as a consequence of passive inclusion. This absence may be related to the alkaline environment typical of struvite stone growth. The finding that UPTF1 is present in some renal stones provides the first direct evidence that links blood coagulation proteins with urolithiasis.  相似文献   
988.
    
Cytotoxic T lymphocytes (CTLs) and natural killers (NK) cells provide immune surveillance against viruses and neoplasms, and play a central role in the pathogenesis of autoimmune disease, AIDS and graft rejection. Thus, it is important to understand the precise molecular mechanism(s) whereby cytotoxic lymphocytes destroy susceptible target cells. Granule-mediated cytotoxicity requires a combination of both perforin and granzyme B. Perforin polymerizes to form transmembrane channels and presumably allows granzyme B access to target cell substrates, which until recently, were unknown. One clue to the identity of the physiological substrate(s) activated by granzyme B comes from its unusual specificity for cleaving synthetic substrates after aspartate residues. Members of the ICE/CED-3 family of cysteine proteases are prime candidates as they are important apoptotic effectors and are expressed as zymogens, which can be processed to form active heterodimeric enzymes after cleavage at specific aspartate residues. Previous studies have shown that granzyme B proteolytically activates the cell death effector Yama/CPP32/apopain (referred to here as Yama). Here we report that granzyme B also activates ICE-LAP3/Mch3/CMH-1 (referred to here as ICE-LAP3), which, along with Yama and Mch2, forms a subset of the ICE/CED-3 family of cysteine proteases most closely related to the Caenorhabditis elegans cell death gene, CED-3. Importantly, Jurkat T cells incubated with granzyme B and a sublytic concentration of perforin undergo apoptosis, which is preceded by the activation of endogenous ICE-LAP3. Thus, we propose that granzyme B mediates apoptosis by directly engaging the target cell's death effector machinery, which is probably composed of an arsenal of intracellular, CED-3-like cysteine proteases.  相似文献   
989.
Lactose intolerance (LI) often results in decreased calcium intake. To test if long-term low intake of calcium affects bone strength, we examined fracture risks related to LI in women aged 38-57 years. The 11,619 Finnish women aged 47-56 years who responded to the baseline postal inquiry of the Kuopio Osteoporosis Risk Factor and Prevention Study in 1989 formed the study population. In all, 896 women reported LI and 1299 women reported a fracture in 1980-1989. Current intake of dairy calcium was lower in women with LI (570 mg/d) than in the other women (850 mg/d) (p < 0.0001). The fracture risk in general was slightly elevated in women with LI compared with the other women, with an odds ratio (OR) (95% CI) of 1.33 (1.09-1.62). However, the fractures at the three most common sites (wrist, ankle, and rib) were not related to LI. In contrast, fractures at the tibia and metatarsal were strongly related to LI with ORs of 3.31 (1.51-7.24) and 2.84 (1.47-5.50), respectively. The adjusted OR for nonankle lower body fractures combined was 2.15 (1.53-3.04), whereas that for all upper body fractures combined was 1.15 (0.88-1.54). The 10 women with LI and a tibial or metatarsal fracture showed a 19% lower femoral BMD than all the other women in the densitometry subsample of 3222 women (p < 0.001). Long-term premenopausal calcium deficiency differentially affects bones with weight-bearing nonankle bones being at the greatest risk of suffering reduced strength.  相似文献   
990.
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