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91.
Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans 总被引:10,自引:3,他引:10
Recent studies of mitochondrial DNA (mtDNA) variation in mammals and
Drosophila have shown an excess of amino acid variation within species
(replacement polymorphism) relative to the number of silent and replacement
differences fixed between species. To examine further this pattern of
nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5
genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans.
Of interest are the frequency spectra of silent and replacement
polymorphisms, and potential variation among genes and taxa in the
departures from neutral expectations. The Drosophila ND3 and ND5 data show
no significant excess of replacement polymorphism using the
McDonald-Kreitman test. These data are in contrast to significant
departures from neutrality for the ND3 gene in mammals and other genes in
Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however,
both Drosophila and human mtDNA show very significant excesses of amino
acid polymorphism. Silent polymorphisms at ND5 show a significantly higher
variance in frequency than replacement polymorphisms, and the latter show a
significant skew toward low frequencies (Tajima's D = -1.954). These
patterns are interpreted in light of the nearly neutral theory where mildly
deleterious amino acid haplotypes are observed as ephemeral variants within
species but do not contribute to divergence. The patterns of polymorphism
and divergence at charge-altering amino acid sites are presented for the
Drosophila ND5 gene to examine the evolution of functionally distinct
mutations. Excess charge-altering polymorphism is observed at the carboxyl
terminal and excess charge-altering divergence is detected at the amino
terminal. While the mildly deleterious model fits as a net effect in the
evolution of nonrecombining mitochondrial genomes, these data suggest that
opposing evolutionary pressures may act on different regions of
mitochondrial genes and genomes.
相似文献
92.
Manfred Keller Andras Seregi Georg Hertting Rolf Jackisch 《Neurochemistry international》1987,10(4):433-443
Prostaglandin (PG) and thromboxane B2 (TXB2) biosynthesis was studied in cultured astrocytes from neonatal rat brain hemispheres. After two weeks of cultivation, prostanoids were formed with the spectrum: PGD2 > TXB2 > PGF2 > PGE2, as measured by specific radioimmunoassays. Under basal conditions PGD2 biosynthesis (9.55 ng/mg protein/15 min) was in the same order of magnitude as the sum of the other prostanoids. The formation of prostanoids was stimulated in a concentration dependent manner (up to 6–10 fold) by the calcium ionophore A 23187 (0.01–10 μM) as well as by melittin (0.01–5 μg/ml), phospholipase A2 (10–40 U/ml) and phospholipase C (0.01–1 U/ml). Basal and evoked PG and TXB2 biosynthesis depended on the availability of Ca2+, as demonstrated in Ca2+ free incubation medium containing Na2EDTA (1 μM), or with verapamil (100 μM) and 3,4,5-trimethoxybenzoic acid-8-(diethylamino)-octylester-HCl (TMB-8, 1–100 μM). Indomethacin (10 μM), mepacrine (100 μM) and p-bromophenacylbromide (50 μ M) inhibited basal and evoked PG formation. Thin-layer chromatography (TLC) detection after incubation of the cells with [3H]arachidonic acid (1 μCi/ml, for 60 min) confirmed the results obtained by radioimmunoassay. Incubation of [3H]arachidonic acid labelled cells with inonophore or phospholipases, followed by lipid extraction and TLC, showed that A 23187 liberated [3H]arachidonic acid predominantly from phosphatidylethanolamine, whereas phospholipase A2 and C reduced mainly the labelling of the phosphatidyl-inositol/-choline fraction. Potassium depolarization of the cells did not enhance prostanoid formation. Similarly, drugs with affinity to - or β-adrenoceptors, or to dopamine-, 5-hydroxytryptamine-, muscarine-, histamine-, glutamate-, aspartate-, GABA, adenosine- and opioid-receptors failed to stimulate prostanoid biosynthesis. Also compounds like angiotensin, bradykinin and thrombin were ineffective in this respect.
In conclusion, our results confirm that cultured astrocytes possess the complete pattern of enzymes necessary for prostanoid formation and hence might play a crucial role in brain prostanoid biosynthesis. Stimulation of prostanoid biosynthesis involves Ca2+-dependent activation of phospholipase A2, cyclooxygenase reaction and further PG metabolism. However, the endogenous stimulus for enhanced prostanoid synthesis in the brain still has to be established. 相似文献
93.
Lim J Menon V Bitzer M Miller LM Madrid-Aliste C Weiss LM Fiser A Angeletti RH 《Analytical biochemistry》2011,(1):78-84
Differential detergent fractionation (DDF) is frequently used to partition fresh cells and tissues into distinct compartments. We have tested whether DDF can reproducibly extract and fractionate cellular protein components from frozen tissues. Frozen kidneys were sequentially extracted with three different buffer systems. Analysis of the three fractions with liquid chromatography–tandem mass spectrometry (LC–MS/MS) identified 1693 proteins, some of which were common to all fractions and others of which were unique to specific fractions. Normalized spectral index (SIN) values obtained from these data were compared to evaluate both the reproducibility of the method and the efficiency of enrichment. SIN values between replicate fractions demonstrated a high correlation, confirming the reproducibility of the method. Correlation coefficients across the three fractions were significantly lower than those for the replicates, supporting the capability of DDF to differentially fractionate proteins into separate compartments. Subcellular annotation of the proteins identified in each fraction demonstrated a significant enrichment of cytoplasmic, cell membrane, and nuclear proteins in the three respective buffer system fractions. We conclude that DDF can be applied to frozen tissue to generate reproducible proteome coverage discriminating subcellular compartments. This demonstrates the feasibility of analyzing cellular compartment-specific proteins in archived tissue samples with the simple DDF method. 相似文献
94.
95.
96.
An evolutionary theory of socialization suggests that children from father-absent families will mature earlier, and form less-stable pair bonds, compared with those from father-present families. Using a sample of about 1,000 persons the recent study focuses on elements of father-absent children’s behavior that could be better explained by a Darwinian approach than by rival social science theories. As a result of their enhanced interest in male competition, father-absent boys were found to engage in rule-breaking behavior more intensively than father-present boys. Compared with father-present children, adolescents from widowed households (both boys and girls) showed a higher intensity of various kinds of noncompliant behavior, which can be linked to their earlier maturation. School attendance, age at marriage, and marital success proved to be influenced by the children’s early family experiences, governed by adapted evolutionary strategies. Father-absent daughters conceived more children than those whose fathers were present during their childhood. As evolutionary theory predicts, reproductive behavior of individuals from divorced households differed from that of individuals who grew up in widowed households. Finally, the strong correlation found between spontaneous abortion/stillbirths and family arrangement indicates that father absence has certain direct impacts on the neurohormonal processes of child development. 相似文献
97.
Three satellite DNA families were identified in three species of burying
beetles, Nicrophorus orbicollis, N. marginatus, and N. americanus. Southern
hybridization and nucleotide sequence analysis of individual randomly
cloned repeats shows that these satellite DNA families are highly abundant
in the genome, are composed of unique repeats, and are species-specific.
The repeats do not have identifiable core elements or substructures that
are similar in all three families, and most interspecific sequence
similarity is confined to homopolymeric runs of A and T. Satellite DNA from
N. marginatus and N. americanus show single-base-pair indels among repeats,
but single-nucleotide substitutions characterize most of the repeat
variability. Although the repeat units are of similar lengths (342, 350,
and 354 bp) and A + T composition (65%, 71%, and 71%, respectively), the
average nucleotide divergence among sequenced repeats is very low (0.18%,
1.22%, and 0.71%, respectively). Transition/transversion ratios from the
consensus sequence are 0.20, 0.69, and 0.70, respectively.
相似文献
98.
W1282X is a common nonsense mutation among cystic fibrosis patients that results in the production of a truncated Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. Here we show that the channel activity of the W1282X-CFTR polypeptide is exceptionally low in excised membrane patches at normally saturating doses of ATP and PKA (single channel open probability (PO) < 0.01). However, W1282X-CFTR channels were stimulated by two CFTR modulators, the FDA-approved VX-770 and the dietary compound curcumin. Each of these compounds is an allosteric modulator of CFTR gating that promotes channel activity in the absence of the native ligand, ATP. Although W1282X-CFTR channels were stimulated by VX-770 in the absence of ATP their activities remained dependent on PKA phosphorylation. Thus, activated W1282X-CFTR channels should remain under physiologic control by cyclic nucleotide signaling pathways in vivo. VX-770 and curcumin exerted additive effects on W1282X-CFTR channel gating (opening/closing) in excised patches such that the Po of the truncated channel approached unity (> 0.9) when treated with both modulators. VX-770 and curcumin also additively stimulated W1282X-CFTR mediated currents in polarized FRT epithelial monolayers. In this setting, however, the stimulated W1282X-CFTR currents were smaller than those mediated by wild type CFTR (3–5%) due presumably to lower expression levels or cell surface targeting of the truncated protein. Combining allosteric modulators of different mechanistic classes is worth considering as a treatment option for W1282X CF patients perhaps when coupled with maneuvers to increase expression of the truncated protein. 相似文献
99.
Membrane resistance change of the frog taste cells in response to water and Nacl 总被引:2,自引:0,他引:2 下载免费PDF全文
The electrical properties of the frog taste cells during gustatory stimulations with distilled water and varying concentrations of NaCl were studied with intracellular microelectrodes. Under the Ringer adaptation of the tongue, two types of taste cells were distinguished by the gustatory stimuli. One type, termed NaCl-sensitive (NS) cells, responded to water with hyperpolarizations and responded to concentrated NaCl with depolarizations. In contrast, the other type of cells, termed water-sensitive (WS) cells, responded to water depolarizations and responded to concentrated NaCl with hyperpolarizations. The membrane resistance of both taste cell types increased during the hyperpolarizing receptor potentials and decreased during the depolarizing receptor potentials, Reversal potentials for the depolarizing and hyperpolarizing responses in each cell type were a few millivolts positive above the zero membrane potential. When the tongue was adapted with Na-free Ringer solution for 30 min, the amplitude of the depolarizing responses in the NS cells reduced to 50% of the control value under normal Ringer adaptation. On the basis of the present results, it is concluded (a) that the depolarizing responses of the NS and WS cells under the Ringer adaptation are produced by the permeability increase in some ions, mainly Na+ ions across the taste cell membranes, and (b) that the hyperpolarizing responses of both types of taste cells are produced by a decrease in the cell membrane permeability to some ions, probably Na+ ions, which is slightly enhanced during the Ringer adaptation. 相似文献
100.
Andras Falus Edward K. Wakeland Thomas J. McConnell Jonathan Gitlin Alexander S. Whitehead Harvey R. Colten M. D. 《Immunogenetics》1987,25(5):290-298
Genes encoding the second component (C2), factor B, and complement protein C4 and Slp (sex-limited protein) are members of the major histocompatibility complex class III gene cluster. In this report we describe isolation of a mouse C2 cDNA clone and its use together with factor B and C4 cDNA clones to examine the S region in a panel of 42 haplotypes in laboratory and wild mice representing 5 species and subspecies of Mus. Conservation of the C2 factor B gene duplex was evidenced by relatively limited polymorphism associated with speciation and nucleotide sequence homology between mouse and human C2 and factor B The C4-Slp gene duplex, on the other hand, showed extensive polymorphism by DNA blot analysis. This polymorphism correlated poorly with the C2/factor B restriction fragment length polymorphism, suggesting independent evolution of these two segments of the S region. Taken together, these data will be of particular importance in studies of mouse strains with abnormal regulation of immune effector systems since the class III gene products are essential for activation of the complement cascade. 相似文献