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101.
102.
103.
Coronary angiography (CAG) was performed in the acute period of myocardial infarction in 41 patients using verografin and in 38 patients using omnipack. In a high risk of CAG performance the tolerance of omnipack was better than that of verografin. Omnipack causes allergic reactions less frequently, disturbs less azote excretory function of the kidneys and myocardial bioelectric activity. 相似文献
104.
Elena Molokanova Alexei Savchenko Richard H. Kramer 《The Journal of general physiology》1999,113(1):45-56
Rod photoreceptor cyclic nucleotide–gated (CNG) channels are modulated by tyrosine phosphorylation. Rod CNG channels expressed in Xenopus oocytes are associated with constitutively active protein tyrosine kinases (PTKs) and protein tyrosine phosphatases that decrease and increase, respectively, the apparent affinity of the channels for cGMP. Here, we examine the effects of genistein, a competitive inhibitor of the ATP binding site, on PTKs. Like other PTK inhibitors (lavendustin A and erbstatin), cytoplasmic application of genistein prevents changes in the cGMP sensitivity that are attributable to tyrosine phosphorylation of the CNG channels. However, unlike these other inhibitors, genistein also slows the activation kinetics and reduces the maximal current through CNG channels at saturating cGMP. These effects occur in the absence of ATP, indicating that they do not involve inhibition of a phosphorylation event, but rather involve an allosteric effect of genistein on CNG channel gating. This could result from direct binding of genistein to the channel; however, the time course of inhibition is surprisingly slow (>30 s), raising the possibility that genistein exerts its effects indirectly. In support of this hypothesis, we find that ligands that selectively bind to PTKs without directly binding to the CNG channel can nonetheless decrease the effect of genistein. Thus, ATP and a nonhydrolyzable ATP derivative competitively inhibit the effect of genistein on the channel. Moreover, erbstatin, an inhibitor of PTKs, can noncompetitively inhibit the effect of genistein. Taken together, these results suggest that in addition to inhibiting tyrosine phosphorylation of the rod CNG channel catalyzed by PTKs, genistein triggers a noncatalytic interaction between the PTK and the channel that allosterically inhibits gating. 相似文献
105.
Using an immunohistochemistry technique, combined with light and electron microscopy,in vitro development of various cell elements in organotypic hippocampal rat slice culture were studied. It was shown that hippocampal
neurons preserve their normal structure and function for a month of culturing. Astrocytes are activated and fulfill a protective
function, and microglial cells show typical dynamics of the development in culture. After experimental hypoxia, progressive
neuronal degradation and death, as well as microglial activation, are observed. The prospects for using hippocampal slice
culture as a model system for studying cellular and molecular mechanisms of brain damage of different etiology are discussed. 相似文献
106.
The topographic distribution of DNA-synthesizing and divisible hepatocytes was studied in the hepatic lobe of intact rats during the 24-hours. For this purpose the indices of a number of DNA-synthesizing and divisible cells were determined both in a liver as a whole and for each lobe zone (periportal, middle and central one). The obtained results allowed to reveal the presence of the 24-hour rhythm of cell proliferation process in a liver as well as the regular topographic distribution of DNA-synthesizing and divisible hepatocytes during the period of their increased values in the rhythm. The process of activation of proliferation seems to start in the periportal zone, and then to hold the whole zone, with its dominance in the middle zone during the period of maximum values of the cell proliferation indices. One could suppose that this testifies to the equal proliferative potencies of hepatocytes irrespective of their localization as well as to the fact that the cells of all zones take part in the formation of acrophases of rhythms both of the DNA-synthesizing hepatocytes and divisible ones. However, the degree of their participation in this process is unequal and depends on the localization of cells in the hepatic lobe. 相似文献
107.
Lunev E. A. Shmidt A. A. Vassilieva S. G. Savchenko I. M. Loginov V. A. Marina V. I. Egorova T. V. Bardina M. V. 《Molecular Biology》2022,56(4):559-571
Molecular Biology - GNAO1 encephalopathy is an orphan genetic disease associated with early infantile epilepsy, impaired motor control, and severe developmental delay. The disorder is caused by... 相似文献
108.
Greg Brown Alexander Singer Vladimir V. Lunin Michael Proudfoot Tatiana Skarina Robert Flick Samvel Kochinyan Ruslan Sanishvili Andrzej Joachimiak Aled M. Edwards Alexei Savchenko Alexander F. Yakunin 《The Journal of biological chemistry》2009,284(6):3784-3792
Gluconeogenesis is an important metabolic pathway, which produces glucose
from noncarbohydrate precursors such as organic acids, fatty acids, amino
acids, or glycerol. Fructose-1,6-bisphosphatase, a key enzyme of
gluconeogenesis, is found in all organisms, and five different classes of
these enzymes have been identified. Here we demonstrate that Escherichia
coli has two class II fructose-1,6-bisphosphatases, GlpX and YggF, which
show different catalytic properties. We present the first crystal structure of
a class II fructose-1,6-bisphosphatase (GlpX) determined in a free state and
in the complex with a substrate (fructose 1,6-bisphosphate) or inhibitor
(phosphate). The crystal structure of the ligand-free GlpX revealed a compact,
globular shape with two α/β-sandwich domains. The core fold of GlpX
is structurally similar to that of Li+-sensitive phosphatases
implying that they have a common evolutionary origin and catalytic mechanism.
The structure of the GlpX complex with fructose 1,6-bisphosphate revealed that
the active site is located between two domains and accommodates several
conserved residues coordinating two metal ions and the substrate. The third
metal ion is bound to phosphate 6 of the substrate. Inorganic phosphate
strongly inhibited activity of both GlpX and YggF, and the crystal structure
of the GlpX complex with phosphate demonstrated that the inhibitor molecule
binds to the active site. Alanine replacement mutagenesis of GlpX identified
12 conserved residues important for activity and suggested that
Thr90 is the primary catalytic residue. Our data provide insight
into the molecular mechanisms of the substrate specificity and catalysis of
GlpX and other class II fructose-1,6-bisphosphatases.Fructose-1,6-bisphosphatase
(FBPase,2 EC
3.1.3.11), a key enzyme of gluconeogenesis, catalyzes the hydrolysis of
fructose 1,6-bisphosphate to form fructose 6-phosphate and orthophosphate. It
is the reverse of the reaction catalyzed by phosphofructokinase in glycolysis,
and the product, fructose 6-phosphate, is an important precursor in various
biosynthetic pathways (1). In
all organisms, gluconeogenesis is an important metabolic pathway that allows
the cells to synthesize glucose from noncarbohydrate precursors, such as
organic acids, amino acids, and glycerol. FBPases are members of the large
superfamily of lithium-sensitive phosphatases, which includes three families
of inositol phosphatases and FBPases (the phosphoesterase clan CL0171, 3167
sequences, Pfam data base). These enzymes show metal-dependent and
lithium-sensitive phosphomonoesterase activity and include inositol
polyphosphate 1-phosphatases, inositol monophosphatases (IMPases),
3′-phosphoadenosine 5′-phosphatases (PAPases), and enzymes acting
on both inositol 1,4-bisphosphate and PAP (PIPases)
(2). They possess a common
structural core with the active site lying between α+β and
α/β domains (3).
Li+-sensitive phosphatases are putative targets for lithium therapy
in the treatment of manic depressive patients
(4), whereas FBPases are
targets for the development of drugs for the treatment of noninsulin-dependent
diabetes (5,
6). In addition, FBPase is
required for virulence in Mycobacterium tuberculosis and
Leishmania major and plays an important role in the production of
lysine and glutamate by Corynebacterium glutamicum
(7,
8).Presently, five different classes of FBPases have been proposed based on
their amino acid sequences (FBPases I to V)
(9–11).
Eukaryotes contain only the FBPase I-type enzyme, but all five types exist in
various prokaryotes. Types I, II, and III are primarily in bacteria, type IV
in archaea (a bifunctional FBPase/inositol monophosphatase), and type V in
thermophilic prokaryotes from both domains
(11). Many organisms have more
than one FBPase, mostly the combination of types I + II or II + III, but no
bacterial genome has a combination of types I and III FBPases
(9). The type I FBPase is the
most widely distributed among living organisms and is the primary FBPase in
Escherichia coli, most bacteria, a few archaea, and all
eukaryotes (9,
11–15).
The type II FBPases are represented by the E. coli GlpX and FBPase
F-I from Synechocystis PCC6803
(9,
16); type III is represented
by the Bacillus subtilis FBPase
(17); type IV is represented
by the dual activity FBPases/inosine monophosphatases FbpA from Pyrococcus
furiosus (18), MJ0109
from Methanococcus jannaschii
(19), and AF2372 from
Archaeoglobus fulgidus
(20); and type V is
represented by the FBPases TK2164 from Pyrococcus
(Thermococcus) kodakaraensis and ST0318 from Sulfolobus
tokodai (10,
21).Three-dimensional structures of the type I (from pig kidney, spinach
chloroplasts, and E. coli), type IV (MJ0109 and AF2372), and type V
(ST0318) FBPases have been solved
(10,
11,
19,
20,
22,
23). FBPases I and IV and
inositol monophosphatases share a common sugar phosphatase fold organized in
five layered interleaved α-helices and β-sheets
(α-β-α-β-α)
(2,
19,
24). ST0318 (an FBPase V
enzyme) is composed of one domain with a completely different four-layer
α-β-β-α fold
(10). The FBPases from these
three classes (I, IV, and V) require divalent cations for activity
(Mg2+, Mn2+, or Zn2+), and their structures
have revealed the presence of three or four metal ions in the active site.E. coli has five Li+-sensitive phosphatases as follows:
CysQ (a PAPase), SuhB (an IMPase), Fbp (a FBPase I enzyme), GlpX (a FBPase
II), and YggF (an uncharacterized protein) (see the Pfam data base). CysQ is a
3′-phosphoadenosine 5′-phosphatase involved in the cysteine
biosynthesis pathway (25,
26), whereas SuhB is an
inositol monophosphatase (IMPase) that is also known as a suppressor of
temperature-sensitive growth phenotypes in E. coli
(27,
28). Fbp is required for
growth on gluconeogenic substrates and probably represents the main
gluconeogenic FBPase (12).
This enzyme has been characterized both biochemically and structurally and
shown to be inhibited by low concentrations of AMP (IC50 15
μm) (11,
29,
30). The E. coli
GlpX, a class II enzyme FBPase, has been shown to possess a
Mn2+-dependent FBPase activity
(9). The increased expression
of glpX from a multicopy plasmid complemented the Fbp-
phenotype; however, the glpX knock-out strain grew normally on
gluconeogenic substrates (succinate or glycerol)
(9).In this study, we present the first structure of a class II FBPase, the
E. coli GlpX, in a free state and in the complex with FBP + metals or
phosphate. We have demonstrated that the fold of GlpX is similar to that of
the lithium-sensitive phosphatases. We have identified the GlpX residues
important for activity and proposed a catalytic mechanism. We have also showed
that YggF is a third FBPase in E. coli, which has distinct catalytic
properties and is more sensitive than GlpX to the inhibition by lithium or
phosphate. 相似文献
109.
P. B. Repin V. D. Selemir V. T. Selyavskiĭ R. V. Savchenko A. P. Orlov B. G. Repin M. Sh. Ibragimov 《Plasma Physics Reports》2009,35(1):42-49
Results are presented from experimental studies and numerical simulations of the effect of preliminary wire explosion on the parameters of X-ray emission generated during wire array Z-pinch implosion. The wire array implosion was driven by a current pulse with an amplitude of 0.5 MA and a rise time of 0.5 μs, while the preliminary wire explosion was produced by a current pulse with an amplitude of 0.5–1 kA per wire, a rise time of 100 ns, and a full width at half maximum of ~200 ns. The experiments showed that the current prepulse significantly impaired the parameters of X-ray pulses. In particular, along with a decrease in the amplitude and an increase in the duration of the X-ray pulse, its spiky structure became more pronounced. The results of numerical simulations with the use of a one-dimensional radiative MHD code are in good agreement with the parameters of Z-pinch emission in experiments with and without a current prepulse. 相似文献
110.
A single tantulus larva was found at the abyssal depth of the Indian Ocean attached to a harpacticoid host of the family Cletodidae. It represents a new genus and species of Tantulocarida, family Basipodellidae. Its ultrastructure was studied with SEM. This genus can be easily distinguished from the other genera of Basipodellidae by the pore pattern, bilobed oral disk with strong longitudinal ridges and the posterior projection of the cephalic shield. A morphological analysis of two related families Basipodellidae and Deothertridae shows that they represent polyphyletic taxa and need further revision. 相似文献