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531.
VF Okhotnikova LK Grakovskaia VG Koroleva GS Minasova IR Zak 《Canadian Metallurgical Quarterly》1976,21(8):719-721
Relation between the rate of tetracycline dissolution from tablets and capsules and the biological acceptibility of the antibiotic in the host was studied. The antibiotic dissolution rate from the pharmaceutical forms was determined in a modernized apparatus "Rotary basket" in water, the speed of the basket rotation was 200 r.p.m. In addition the tetracycline blood levels in patients treated with the drug in the above pharmaceutical forms were estimated. It was found that the rate of the antibiotic dissolution characterized the antibiotic biological acceptibility. A test for the dissolution rate was developed. It may be used for estimation of production batches of tetracycline tablets. 相似文献
532.
Okorokov AL; Panov KI; Offen WA; Mukhortov VG; Antson AA; Karpeisky MYa; Wilkinson AJ; Dodson GG 《Protein engineering, design & selection : PEDS》1997,10(3):273-278
Members of the microbial guanyl-specific ribonuclease family catalyse the
endonucleolytic cleavage of single-stranded RNA in a two-step reaction
involving transesterification to form a 2',3'-cyclic phosphate and its
subsequent hydrolysis to yield the respective 3'-phosphate. The
extracellular ribonuclease from Bacillus intermedius (binase, RNase Bi)
shares a common mechanism for RNA hydrolysis with mammalian RNases. Two
catalytic residues in the active site of binase, Glu72 and His101, are
thought to be involved in general acid-general base catalysis of RNA
cleavage. Using site-directed mutagenesis, binase mutants were produced
containing amino acid substitutions H101N and H101T and their catalytic
properties towards RNA, poly(I), poly(A), GpC and guanosine 2',3'- cyclic
phosphate (cGMP) substrates were studied. The engineered mutant proteins
are active in the transesterification step which produces the 2',3'-cyclic
phosphate species but they have lost the ability to catalyse hydrolysis of
the cyclic phosphate to give the 3' monophosphate product.
相似文献
533.
534.
B Van den Burg G Vriend OR Veltman G Venema VG Eijsink 《Canadian Metallurgical Quarterly》1998,95(5):2056-2060
In recent years, many efforts have been made to isolate enzymes from extremophilic organisms in the hope to unravel the structural basis for hyperstability and to obtain hyperstable biocatalysts. Here we show how a moderately stable enzyme (a thermolysin-like protease from Bacillus stearothermophilus, TLP-ste) can be made hyperstable by a limited number of mutations. The mutational strategy included replacing residues in TLP-ste by residues found at equivalent positions in naturally occurring, more thermostable variants, as well as rationally designed mutations. Thus, an extremely stable 8-fold mutant enzyme was obtained that was able to function at 100 degrees C and in the presence of denaturing agents. This 8-fold mutant contained a relatively large number of mutations whose stabilizing effect is generally considered to result from a reduction of the entropy of the unfolded state ("rigidifying" mutations such as Gly --> Ala, Ala --> Pro, and the introduction of a disulfide bridge). Remarkably, whereas hyperstable enzymes isolated from natural sources often have reduced activity at low temperatures, the 8-fold mutant displayed wild-type-like activity at 37 degrees C. 相似文献
535.
536.
A characteristic feature of heart failure is the progressive worsening of ventricular function over months or years despite the absence of clinically apparent intercurrent adverse events. The mechanism or mechanisms responsible for this hemodynamic deterioration are not known but may be related to progressive intrinsic contractile dysfunction of residual viable cardiac myocytes, or to ongoing degeneration and loss of myocytes, or both. This report will address the concept of ongoing cardiac myocyte loss that may occur during the course of evolving heart failure viewed from the perspective of apoptosis or "programmed cell death" as the potential mediator of cardiac muscle cell loss. In recent years, several studies have shown that constituent myocytes of failed explanted human hearts and hearts of animals with experimentally induced heart failure undergo apoptosis. Recent studies have shown that cardiac myocyte apoptosis also occurs after acute myocardial infarction, as well as in the hypertrophied heart and the aging heart, conditions frequently associated with the development of heart failure. Considerable work has also been conducted and novel concepts advanced to explain potential molecular triggers of cardiac myocyte apoptosis in heart failure. Although available data support the existence of myocyte apoptosis in the failing heart, questions essential to our understanding of the importance of myocyte apoptosis in this disease process remain unanswered. Lacking are studies aimed at identifying physiological factors inherent to heart failure that trigger myocyte apoptosis. Also lacking are studies that address the importance of myocyte apoptosis in the progression of left ventricular dysfunction. If loss of cardiac myocytes through apoptosis can be shown to be an important contributor to the progression of heart failure, and if factors that trigger apoptosis in the heart can be identified, such knowledge can potentially lead to the development of novel therapeutic modalities aimed at preventing, or at the very least retarding, the process of progressive ventricular dysfunction and the ultimate transition toward end-stage, intractable heart failure. 相似文献
537.
538.
II Morozov IP Dergacheva VG Petin BV Dubovik GV Morozova 《Canadian Metallurgical Quarterly》1996,36(5):671-675
The influence of microwaves and heat on dynamics of heating of samples of intact and inactivated bacteria Escherichia coli and solutions of some basic molecular components of cell was investigated. It was shown that microwaves induce different dynamics of heating of all samples. On the contrary, thermal action induces identical dynamics of heating of all this samples except vegetable oil which was heated more intensively. 相似文献
539.
Frigerio F; Margarit I; Nogarotto R; Grandi G; Vriend G; Hardy F; Veltman OR; Venema G; Eijsink VG 《Protein engineering, design & selection : PEDS》1997,10(3):223-230
The present study concerns the use of site-directed mutagenesis experiments
to optimize a three-dimensional model of the neutral protease of Bacillus
subtilis (NP-sub). An initial model of NP-sub was constructed using the
crystal structures of the homologous neutral proteases of Bacillus
thermoproteolyticus (thermolysin) and Bacillus cereus as templates. The
largest portion of NP-sub could be modelled satisfactorily, using standard
techniques, but several surface-located regions could only be modelled with
a high degree of uncertainty. In order to make the model more reliable in
these regions a 'model building by mutagenesis' approach was adopted.
Mutations were designed such that their effect on thermal stability could
indicate how their local environment should be modelled. This approach
provided insight in the local structure of several regions in NP-sub that
were hard to model on the basis of homology with the two known structures
alone.
相似文献