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881.
Abnormal synthesis of dolichol-linked oligosaccharides in carbohydrate-deficient glycoprotein syndrome 总被引:4,自引:2,他引:2
Krasnewich Donna M.; Holt Gordon D.; Brantly Mark; Skovby Flemming; Redwine Jeff; Gahl William A. 《Glycobiology》1995,5(5):503-510
Carbohydrate-deficient glycoprotein syndrome (CDGS) is a raremetabolic disorder presenting in infancy with severe neurologicinvolvement and variable multisystemic abnormalities. Diagnosisrelies upon the detection of abnormal serum glycoprotein isoformson isoelectric focusing (IEF) gels. Carbohydrate structuralanalyses were performed on the N-linked oligosaccharides ofserum 相似文献
882.
Alexander J. Bridges Donna R. Cody Hairong Zhou Amy McMichael David W. Fry 《Bioorganic & medicinal chemistry》1995,3(12)
4-Benzylaminoquinazolines can be potent reversible inhibitors of the EGFR tyrosine kinase at the ATP binding site. Examination of benzylic methylation reveals that an (R)-methyl group is four- to six-fold activating, with an optimal Ki of 630 pM for compound II. In sharp contrast, (S)-methylation causes a > 30 to 500-fold loss of inhibitory activity, showing that the ATP-binding site of the receptor has very low tolerance for even moderate out-of-plane bulk in certain directions. It is suggested that the best of these inhibitors can induce a conformation of the kinase not available to poorer inhibitors. 相似文献
883.
A modified procedure for PCR-based differential display and demonstration of use in plants for isolation of genes related to fruit ripening 总被引:1,自引:1,他引:0
We have modified and optimized PCR-based differential display for efficient identification and isolation of genes whose expression
patterns are correlated with changes in growth, development, physiology, and/or environmental response. This protocol is general
in nature and can be applied for analysis of virtually any plant tissues from which several μg of total RNA can be extracted.
We report here the use of tomato fruit ripening as a model system in which to test and optimize differential display in plants.
Specifically, mRNA from ripe, early breaker, mature green, and ethylene-treated mature green tomato fruit were examined to
identify and distinguish non-ethylene-inducible from ethylene-inducible genes related to ripening. DNA-free total RNA was
utilized as template for synthesis of first-strand complementary DNA using each of 12 possible 5′-T11 XY-3′ anchor primers (X=A, C, or G; Y=A, C, G, or T). PCR amplification products of the resulting cDNA populations were generated
via use of random primers in combination with the corresponding anchor primer employed for cDNA synthesis. We demonstrate
that degenerative anchor primers are useful for making representative cDNA populations, but are not effective for representative
display-PCR. cDNA, resulting from degenerative anchor primer synthesis, yielded substantially fewer ripening-related display-PCR
products when amplified with the same degenerative anchor primer employed in cDNA synthesis, versus the corresponding set
of specific anchor primers. Amplification products specific to ripe fruit cDNA were isolated directly from display gels, reamplified,
cloned, and confirmed for ripening-related gene expression via RNA gel-blot analysis. 相似文献
884.
885.
Hirotaka Yamamoto Yoichi Kaneko David Vandermulen Donna Kersey Edward Mkrdichian Leonard Cerullo Jan Leestma Joseph R. Moskal 《Glycoconjugate journal》1995,12(6):848-856
The expression of CMP-NeuAc: Gal1,4GlcNAc 2,6 sialyltransferase (2,6-ST) [EC 2.4.99.1] and glycoproteins bearing 2,6-linked sialic acids were examined in primary human brain tumours and cell lines. 79% (19/24) of the meningiomas expressed 2,6-ST mRNA, 42% (10/24) of which showed very high expression. 2,6-ST mRNA expression was undetectable in normal brain tissue. In contrast, only 1/13 of the gliomas examined expressed detectable 2,6-ST mRNA. Metastases to the brain did not express measurable amounts of 2,6-ST mRNA. Less expression was found in malignant (i.e., anaplastic) compared to benign (i.e. meningothelial) meningiomas. Two-dimensional SDS-PAGE of glioma and meningioma proteins, followed bySambucus nigra lectin staining, revealed the presence of a glycoprotein bearing 2,6-linked sialic acids,M
r=53 kDa and a pI=7.0 (MEN-1) that appeared in all seven of the meningiomas examined, but was expressed at barely detectable levels, if at all, in seven out of the seven glioblastomas examined. Thus, decreased 2,6-ST expression may play a role in the aggressive nature of anaplastic meningiomas, but appears to be virtually absent in all tumours of glial origin. 相似文献
886.
Theresa A. Harrison Harriett A. Stadt Donna Kumiski Margaret L. Kirby 《Cell and tissue research》1995,281(2):379-385
The nodose ganglion is the distal cranial ganglion of the vagus nerve which provides sensory innervation to the heart and other viscera. In this study, removal of the neuronal precursors which normally populate the right nodose ganglion was accomplished by ablating the right nodese placode in stage 9 chick embryos. Subsequent histological evaluation showed that in 54% of lesioned embryos surviving to day 6, the right ganglion was absent. Most embryos surviving to day 12, however, had identifiable right ganglia. In day 12 embryos, the right ganglion which developed was abnormal, with ganglion volume and ganglion cell diameter reduced by 50% and 20%, respectively, compared to control ganglia. To investigate the source of the neuron population in the regenerated ganglion, we combined nodose placode ablation with bilateral replacement of chick with quail cardiac neural crest (from mid-otic placode to somite 3). These cells normally provide only non-neuronal cells to the nodose ganglion, but produce neurons in other regions. At day 9, quail-derived neurons were identified in the right nodose ganglia of these chimeras, indicating that cardiac neural crest cells can generate neurons in the ganglion when placode-derived neurons are absent or reduced in number. On the other hand, we found that sympathetic neural crest (from somites 10 to 20) does not support ganglion development, suggesting that only neural crest cells normally present in the ganglion participate in reconstituting its neuronal population. Our previous work has shown that right nodose placode ablation produces abnormal cardiac function, which mimics a life-threatening human heart condition known as long QT syndrome. The present results suggest that the presence of neural crest-derived neurons in the developing right nodose ganglion may contribute to the functional abnormality in long QT syndrome.This work was supported by grant PO1 HL 36059 相似文献
887.
The effectiveness of chemiluminescence (ChL) in vitro to measure free radicals generated as a result of metabolic disorganization
caused by radiation sickness is evaluated. The results are correlated with those obtained by measuring superoxide dismutase
(SOD) activity and lipid peroxide as levels of thiobarbituric acid reacting substances (TBARS).
To this aim, livers from irradiated Wistar rats were removed immediately (day 0) after irradiation and also 7 and 14 d later.
ChL results, expressed in arbitrary units (AU)/min/mg protein, were analyzed for irradiated samples and controls, for different
doses at different times. Increased levels of ChL emission were observed not only on day 0, but also on days 7 and 14. On
the other hand, SOD activity showed a decrease on the 7th d, and significantly higher lipid peroxide levels were observed
in the assays performed on the 14th d, at all exposure doses. The correlation between temporal changes in the SOD activity,
ChL emission, and higher TBARS levels a week later were evident from the data.
These results indicate that the ChL technique proved to be useful in combination with other techniques currently used for
evaluating radiation oxidative injury. 相似文献
888.
A Role for the p38 Mitogen-activated Protein Kinase Pathway in Myocardial Cell Growth, Sarcomeric Organization, and Cardiac-specific Gene Expression 总被引:21,自引:0,他引:21
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Dietmar Zechner Donna J. Thuerauf Deanna S. Hanford Patrick M. McDonough Christopher C. Glembotski 《The Journal of cell biology》1997,139(1):115-127
Three hallmark features of the cardiac hypertrophic growth program are increases in cell size, sarcomeric organization, and the induction of certain cardiac-specific genes. All three features of hypertrophy are induced in cultured myocardial cells by α1- adrenergic receptor agonists, such as phenylephrine (PE) and other growth factors that activate mitogen- activated protein kinases (MAPKs). In this study the MAPK family members extracellular signal–regulated kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 were activated by transfecting cultured cardiac myocytes with constructs encoding the appropriate kinases possessing gain-of-function mutations. Transfected cells were then analyzed for changes in cell size, sarcomeric organization, and induction of the genes for the A- and B-type natriuretic peptides (NPs), as well as the α-skeletal actin (α-SkA) gene. While activation of JNK and/or ERK with MEKK1COOH or Raf-1 BXB, respectively, augmented cell size and effected relatively modest increases in NP and α-SkA promoter activities, neither upstream kinase conferred sarcomeric organization. However, transfection with MKK6 (Glu), which specifically activated p38, augmented cell size, induced NP and α-Ska promoter activities by up to 130-fold, and elicited sarcomeric organization in a manner similar to PE. Moreover, all three growth features induced by MKK6 (Glu) or PE were blocked with the p38-specific inhibitor, SB 203580. These results demonstrate novel and potentially central roles for MKK6 and p38 in the regulation of myocardial cell hypertrophy. 相似文献
889.
Rapid Retrograde Tyrosine Phosphorylation of
trkA and Other Proteins in Rat
Sympathetic Neurons in Compartmented Cultures 总被引:12,自引:0,他引:12
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According to the current theory of retrograde signaling, NGF binds to receptors on the axon terminals and is internalized by receptor-mediated endocytosis. Vesicles with NGF in their lumina, activating receptors in their membranes, travel to the cell bodies and initiate signaling cascades that reach the nucleus. This theory predicts that the retrograde appearance of activated signaling molecules in the cell bodies should coincide with the retrograde appearance of the NGF that initiated the signals. However, we observed that NGF applied locally to distal axons of rat sympathetic neurons in compartmented cultures produced increased tyrosine phosphorylation of trkA in cell bodies/ proximal axons within 1 min. Other proximal proteins, including several apparently localized in cell bodies, displayed increased tyrosine phosphorylation within 5–15 min. However, no detectable 125I-NGF appeared in the cell bodies/proximal axons within 30–60 min of its addition to distal axons. Even if a small, undetectable fraction of transported 125I-NGF was internalized and loaded onto the retrograde transport system immediately after NGF application, at least 3–6 min would be required for the NGF that binds to receptors on distal axons just outside the barrier to be transported to the proximal axons just inside the barrier. Moreover, it is unlikely that the tiny fraction of distal axon trk receptors located near the barrier alone could produce a measurable retrograde trk phosphorylation even if enough time was allowed for internalization and transport of these receptors. Thus, our results provide strong evidence that NGF-induced retrograde signals precede the arrival of endocytotic vesicles containing the NGF that induced them. We further suggest that at least some components of the retrograde signal are carried by a propagation mechanism. 相似文献
890.
Paul Harmon Donna Cabral-Lilly Robert A. Reed Frank P. Maurio J.Craig Franklin Andrew Janoff 《Analytical biochemistry》1997,250(2):139
Incorporation of lipopolysaccharide (LPS) into liposomes dramatically reduces its ability to coagulateLimulusamebocyte lysate (LAL). The coagulation of LAL is commonly used to signal the presence of endotoxinin vitro.This study demonstrates a simple method to release masked endotoxin from liposomal dispersions using moderate amounts of detergent to form mixed micelles containing lipid, detergent, and LPS. Several parameters were found to affect the degree of liposome solubilization and/or the sensitivity of the LAL assay. These included detergent type and concentration, temperature for solubilization, lipid composition, liposome morphology, and time for test incubation. The nonionic detergent polyoxyethylene 10 lauryl ether (C12E10) proved to be unique in its ability to solubilize liposomes and minimally interfere with endotoxin detection. The LAL endotoxin detection limit for samples dispersed in C12E10varied with the phospholipid component; the sensitivity decreased in the order DSPC > DPPC = EPC DMPC. Cholesterol lowered the solubility limit of the liposomes, but did not appear to affect the LAL assay sensitivity once the liposomes were completely solubilized. The presence of negatively charged phospholipids, DSPG and Pops, also lowered the solubility limit. Pops, but not DSPG, at 10 mol% further decreased the LAL endotoxin detection limit. This detergent-solubilization method should be useful in liposomal LPS immunological studies or in other situations where accurate determination of endotoxin concentration is important. 相似文献