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991.
In the adult Drosophila ovary the continuous production of eggs depends upon a small group of stem cells located at the anterior tip of the germarium. These stem cells divide asymmetrically to self renew and to generate a cystoblast, which in females is committed to the oocyte differentiation pathway. While much is known about the development of poststem cell cystoblasts, little is known about when stem cells are formed or how their identity is initially established. To investigate these questions we have used the P-M hybrid dysgenesis syndrome as a tool for ablating the "pre-stem cell" progenitors of the stem cells. Our experiments indicate that the pre-stem cells in females assume stem cell identity during the early pupal stage. Our results also suggest a model in which at least two pre-stem cells must be present within an ovariole for the specification of stem cell fate. When only a single pre-stem cell is sequestered by an ovariole, this cell does not assume stem cell identity, but instead follows the cystoblast-cystocyte differentiation pathway. 相似文献
992.
The peripheral blood monocyte is the reactive cell in the tube LAI assay. The monocyte loses its properties of adherence to glass upon exposure to specific antigen. Two different experiments to determine if lymphocytes, when they reacted with tumour, released mediators that were responsible for inhibiting monocyte glass adherence, gave negative results. The mechanism wherby the specific tumour antigen appeared to be recognized was the binding of cytophilic IgG antitumour antibody to receptors on the cell surface of the monocyte. The results of the experiments indicate that normal peripheral blood monocytes could be made specifically reactive ("armed") to the tumour extract by incubating normal peripheral blood leukocytes with serum from a reactive cancer patient. IgG isolated from "arming" sera was shown to have the capacity to sensitize normal leukocytes. Patients with breast cancer or malignant melanoma with limited tumour burdens had free cytophilic anti-tumour antibody in their serum, whereas the serum of patients with large tumour burdens (metastatic cancer), whose leukocytes did not react in the tube LAI assay, did not "arm". 相似文献
993.
DM Cosgrove JF Sabik JL Navia 《Canadian Metallurgical Quarterly》1998,65(6):1535-8; discussion 1538-9
BACKGROUND: To reduce the morbidity from valvular heart operations, a right parasternal approach was introduced. We report our initial experience with the procedure. METHODS: From January 1996 through July 1996, 115 patients underwent primary isolated valve procedures. One hundred (85%) patients underwent the operation through a right parasternal incision. RESULTS: There was one hospital death secondary to a stroke on the fifth postoperative day. Three patients (two with aortic valve operations and one having a mitral valve procedure) required conversion to sternotomy. Mean aortic occlusion time was 71 minutes; mean cardiopulmonary bypass time was 93 minutes. Mean stay in the intensive care unit was 27 hours and mean hospital postoperative stay was 5.7 days. Seventy-seven percent of the patients did not receive blood transfusions. Comparison with median sternotomy demonstrated a reduction in both postoperative length of stay and direct hospital costs. CONCLUSIONS: We conclude that this minimally invasive approach is safe for a variety of valve procedures and is effective in reducing surgical trauma and cost. 相似文献
994.
M Rossi MS Kim DG Morgan CJ Small CM Edwards D Sunter S Abusnana AP Goldstone SH Russell SA Stanley DM Smith K Yagaloff MA Ghatei SR Bloom 《Canadian Metallurgical Quarterly》1998,139(10):4428-4431
Agouti-related protein (Agrp) is present in rat and human hypothalamus and is structurally related to agouti protein. Overexpression of either of these proteins results in obesity. However the effect of exogenous Agrp and its in vivo interaction with alpha-melanocyte stimulating hormone (alphaMSH), the likely endogenous melanocortin 3 and 4 receptor (MC3-R and MC4-R) agonist, have not been demonstrated. We report that 1 nmol of Agrp(83-132), a C-terminal fragment of Agrp, when administered intracerebroventricularly (ICV) into rats, increased food intake over a 24-h period (23.0+/-1.4 g saline vs 32.9+/-2.3 g Agrp, p<0.05). The hyperphagia was similar to that seen when 1 nmol of the synthetic MC3-R and MC4-R antagonist SHU9119 was given i.c.v. (19.6+/-1.8 g saline vs 32.5+/-1.7 g SHU9119, p<0.001). Both Agrp(83-132) and SHU9119 blocked the reduction in 1-h food intake of i.c.v. alphaMSH at the beginning of the dark phase. This effect occurred independently of whether the antagonists were administered simultaneously, or nine hours prior, to the alphaMSH. We have also shown Agrp(83-132) is an antagonist at the MC3-R and MC4-R, with similar inhibition of cAMP activation to that previously reported for the full length peptide. In conclusion, Agrp(83-132) administered i.c.v. increases feeding with long lasting effects and is able to inhibit the action of alphaMSH. This interaction may be mediated by the MC3-R and/or MC4-R. 相似文献
995.
996.
Essential dynamics of lipase binding sites: the effect of inhibitors of different chain length 总被引:1,自引:0,他引:1
Peters GH; van Aalten DM; Svendsen A; Bywater R 《Protein engineering, design & selection : PEDS》1997,10(2):149-158
The biochemical activity of enzymes, such as lipases, is often associated
with structural changes in the enzyme resulting in selective and
stereospecific reactions with the substrate. To investigate the effect of a
substrate and its chain length on the dynamics of the enzyme, we have
performed molecular dynamics simulations of the native Rhizomucor miehei
lipase (Rml) and lipase-dialkylphosophate complexes, where the length of
the alkyl chain ranges from two to 10 carbon atoms. Simulations were
performed in water and trajectories of 400 ps were used to analyse the
essential motions in these systems. Our results indicate that the internal
motions of the Rml and Rml complexes occur in a subspace of only a few
degrees of freedom. A high flexibility is observed in solvent-exposed
segments, which connect beta-sheets and helices. In particular, loop
regions Gly35-Lys50 and Thr57-Asn63 fluctuate extensively in the native
enzyme. Upon activation and binding of the inhibitor, involving the
displacement of the active site loop, these motions are considerably
suppressed. With increasing chain length of the inhibitor, the fluctuations
in the essential subspace increase, levelling off at a chain length of 10,
which corresponds to the size of the active-site groove.
相似文献
997.
Thrombin can activate factor XI in the presence of dextran sulfate or sulfatides. However, a physiological cofactor for thrombin activation of factor XI has not been identified. We examined this question in a cell-based, tissue factor-initiated model system. In the absence of factor XII, factor XI enhanced thrombin generation in this model. The effect on thrombin generation was reproduced by 2 to 5 pmol/L factor XIa. A specific inhibitor of factor XIIa did not diminish the effect of factor XI. Thus, factor XI can be activated in a model system that does not contain factor XIIa or nonphysiological cofactors. Preincubation of factor XI with activated platelets and thrombin or factor Xa enhanced subsequent thrombin generation in the model system. Preincubation of factor XI with thrombin or factor Xa, but without platelets, did not enhance thrombin generation, suggesting that these proteases might activate factor XI on platelet surfaces. Thrombin and factor Xa were then directly tested for their ability to activate factor XI. In the presence of dextran sulfate, thrombin or factor Xa activated factor XI. Thrombin, but not factor Xa, also cleaved detectable amounts of factor XI in the presence of activated platelets. Thus, thrombin activates enough factor XI to enhance subsequent thrombin generation in a model system. Platelet surfaces might provide the site for thrombin activation of functionally significant amounts of factor XI in vivo. 相似文献
998.
MF Fromm B Leake DM Roden GR Wilkinson RB Kim 《Canadian Metallurgical Quarterly》1999,1415(2):369-374
In humans, at least six members of the multidrug resistance-associated protein (MRP) family are thought to exist. Here we report the molecular cloning of two splice variants of MRP3 from human liver. In addition, MRP3 genomic organization including the 5'-flanking region and a major portion of the MRP3 intron-exon organization are identified and characterized. 相似文献
999.
DM Lawrence MM Vaughn AR Belman JS Cole GF Rall 《Canadian Metallurgical Quarterly》1999,73(3):1795-1801
From the biobreeding-diabetic prone (BB-DP) rat, an animal model for endocrine autoimmunity, phenotype and function of splenic dendritic cells (DC) were studied. Furthermore, the suppressive effect of peritoneal macrophages (pMphi) from the BB-DP rat in the MLR was investigated. Lower numbers of splenic DC were isolated from BB-DP rats than from control Wistar rats. In the preautoimmune phase, DC of the BB-DP rat had a lower surface MHC class II expression (and in preliminary data, a lower CD80 expression), ingested more bacteria, and had a lower stimulatory potency in the syngeneic (syn)MLR as compared with control DC. During disease development, the MHC class II expression further decreased, and a low stimulatory activity became evident in the allogeneic (allo)MLR. With regard to the expansion of suppressor/regulatory T cells, a lower percentage of RT6+ T cells but higher percentages of CD45RClow T cells were induced by BB-DP DC in synMLR, but not in alloMLR. An increase in the CD4/CD8 T cell ratio was observed in both the syn- and alloMLR due to a relative weak expansion of CD8+ T cells with DC of the BB-DP rat. Resident pMphi isolated from BB-DP or Wistar rats were equally effective in suppressing the DC-driven synMLR. In conclusion, splenic DC from the BB-DP rat have a lower accessory cell function already at young age, before the development of disease, and expanded different subsets of effector/suppressor T cells in vitro as compared with those from Wistar rats. The dysfunction of DC from BB-DP rats is likely to be caused by their relative immaturity as indicated by their low class II and costimulatory molecule expression and relatively high phagocytic activity. 相似文献
1000.
DM Woodcock ME Linsenmeyer JP Doherty WD Warren 《Canadian Metallurgical Quarterly》1999,79(2):251-256
The p16 (CDKN2/MTS-1/INK4A) gene is one of several tumour-suppressor genes that have been shown to be inactivated by DNA methylation in various human cancers including breast tumours. We have used bisulphite genomic sequencing to examine the detailed sequence specificity of DNA methylation in the CpG island promoter/exon 1 region in the p16 gene in DNA from a series of human breast cancer specimens and normal human breast tissue (from reductive mammaplasty). The p16 region examined was unmethylated in the four normal human breast specimens and in four out of nine breast tumours. In the other five independent breast tumour specimens, a uniform pattern of DNA methylation was observed. Of the nine major sites of DNA methylation in the amplified region from these tumour DNAs, four were in non-CG sequences. This unusual concentration of non-CG methylation sites was not a general phenomenon present throughout the genome of these tumour cells because the methylated CpG island regions of interspersed L1 repeats had a pattern of (almost exclusively) CG methylation similar to that found in normal breast tissue DNA and in DNA from tumours with unmethylated p16 genes. These data suggest that DNA methylation of the p16 gene in some breast tumours could be the result of an active process that generates a discrete methylation pattern and, hence, could ultimately be amenable to therapeutic manipulation. 相似文献