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101.
102.
Bartsch M Zorn-Kruppa M Kühl N Genieser HG Schwede F Jastorff B 《Biological chemistry》2003,384(9):1321-1326
In the present study, the cAMP analogs 8-bromo-cAMP (8-Br-cAMP), N6-2'O-dibutyryl-cAMP (DBcAMP) and 8-para-chlorophenylthio-cAMP (8-CPT-cAMP), as well as the corresponding cAMP-acetoxymethyl (AM)-ester-prodrugs were tested in a HPLC study for their membrane permeability, intracellular accumulation and biotransformation. Antiproliferative activities of these compounds were studied in the rat C6 glioma cell line. Chromatographic analysis revealed that the AM-ester analogs of the cyclic nucleotides penetrate quantitatively into rat C6 glioma cells and generate high amounts of their parent cyclic nucleotides intracellularly within 60 min; however, long-term growth inhibition tested in C6 cells is only slightly enhanced with the AM-ester prodrugs of 8-Br-cAMP or DBcAMP. 相似文献
103.
Allosteric enhancement of the affinity of muscarinic receptors for their ligands offers a new way to influence cholinergic neurotransmission. The structure of the allosteric binding domain(s) and the features of agonists, antagonists and modulators which determine the occurrence of either positive or negative cooperativity require clarification. We tested interactions between allosteric modulators alcuronium, strychnine and brucine and eight antagonists at muscarinic receptors expressed in CHO cells. In experiments with unlabeled antagonists, all three modulators enhanced the affinity for 4-diphenylacetoxy-N-dimethylpiperidinium (4-DAMP) at the M2 receptors, and strychnine did so also at the M4 receptors. Positive interactions were also observed between alcuronium and L-hyoscyamine (M2) and scopolamine (M2), between strychnine and butylscopolamine (M4), L-hyoscyamine (M2 and M4) and scopolamine (M4), and between brucine and scopolamine (M2). Positive effects of alcuronium, strychnine and brucine on the affinity of the M2 receptors for 4-DAMP have been confirmed by direct measurements of the binding of [3H]-4-DAMP. A comparison of molecular models of several antagonists which are esters revealed that antagonists in which the distance between the N and the carboxyl C atoms corresponds to five chemical bonds are more likely to display positive cooperativity with alcuronium at the M2 receptors than the antagonists in which the N-carboxyl C distance corresponds to four chemical bonds. 相似文献
104.
Expression of cucumber lipid-body lipoxygenase in transgenic tobacco: lipid-body lipoxygenase is correctly targeted to seed lipid bodies 总被引:2,自引:0,他引:2
A particular isoform of lipoxygenase (LOX, EC 1.13.11.12) localized on lipid bodies has been shown by earlier investigations
to play a role during seed germination in initiating the mobilization of triacylglycerols. On lipid bodies of germinating
cucumber (Cucumis sativus L.) seedlings, the modification of linoleoyl moieties by this LOX precedes the hydrolysis of the ester bonds. We analyzed
the expression and intracellular location of this particular LOX form in leaves and seeds of tobacco (Nicotiana tabacum L.) transformed with one construct coding for cucumber lipid-body LOX and one construct coding for cucumber LOX fused with
a hemagglutinin epitope. In both tissues, the amount of lipid-body LOX was clearly detectable. Biochemical analysis revealed
that in mature seeds the foreign LOX was targeted to lipid bodies, and the preferred location of the LOX on lipid bodies was
verified by immunofluorescence microscopy. Cells of the endosperm and of the embryo exhibited fluorescence based on the immunodecoration
of LOX protein whereas very weak fluorescent label was visible in seeds of untransformed control plants. Further cytochemical
analysis of transformed plants showed that the LOX protein accumulated in the cytoplasm when green leaves lacking lipid bodies
were analyzed. Increased LOX activity was shown in young leaves of transformed plants by an increase in the amounts of endogenous
(2E)-hexenal and jasmonic acid.
Received: 9 August 1999 / Accepted: 28 September 1999 相似文献
105.
Eriophorum vaginatum and E. angustifolium are dominant arctic sedges of the well-drained tussock tundra and the permanently flooded wet-sedge tundra, respectively. We determined diurnal courses of gas exchange and water relations of the two species in their natural habitat and compared their responses to changes in light, air temperature, and humidity. Mean photosynthetic response to light was similar between E. angustifolium and E. vaginatum and carbon gain in both species was light limited during most of the growing season. On sunny and dry days, both species closed stomata in response to high leaf-to-air vapor pressure deficits. Even though E. angustifolium was growing in standing water, it exhibited a tighter control of transpirational water loss and had lower hydraulic conductivity in the soil-root-shoot pathway than E. vaginatum. The different response pattern between the two species is discussed in the context of differences in habitat conditions. 相似文献
106.
The Drosophila splicing regulator sex-lethal directly inhibits translation of male-specific-lethal 2 mRNA. 总被引:3,自引:1,他引:2
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Male-specific expression of the protein male-specific-lethal 2 (MSL-2) controls dosage compensation in Drosophila. msl-2 gene expression is inhibited in females by Sex-lethal (SXL), an RNA binding protein known to regulate pre-mRNA splicing. An intron present at the 5' untranslated region (UTR) of msl-2 mRNA contains putative SXL binding sites and is retained in female flies. Here we show that SXL plays a dual role in the inhibition of msl-2 expression. Cotransfection of Drosophila Schneider cells with an SXL expression vector and a reporter containing the 5' UTR of msl-2 mRNA resulted in retention of the 5' UTR intron and efficient accumulation of the unspliced mRNA in the cytoplasm, where its translation was blocked by SXL, but not by the intron per se. Both splicing and translation inhibition by SXL were recapitulated in vitro and found to be dependent upon SXL binding to high-affinity sites within the intron, showing that SXL directly regulates these events. Our data reveal a coordinated mechanism for the regulation of msl-2 expression by the same regulatory factor: SXL enforces intron retention in the nucleus and subsequent translation inhibition in the cytoplasm. 相似文献
107.
Interference between Proteins Hap46 and Hop/p60, Which Bind to Different Domains of the Molecular Chaperone hsp70/hsc70 总被引:1,自引:0,他引:1
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Mathias Gebauer Matthias Zeiner Ulrich Gehring 《Molecular and cellular biology》1998,18(11):6238-6244
Several structurally divergent proteins associate with molecular chaperones of the 70-kDa heat shock protein (hsp70) family and modulate their activities. We investigated the cofactors Hap46 and Hop/p60 and the effects of their binding to mammalian hsp70 and the cognate form hsc70. Hap46 associates with the amino-terminal ATP binding domain and stimulates ATP binding two- to threefold but inhibits binding of misfolded protein substrate to hsc70 and reactivation of thermally denatured luciferase in an hsc70-dependent refolding system. By contrast, Hop/p60 interacts with a portion of the carboxy-terminal domain of hsp70s, which is distinct from that involved in the binding of misfolded proteins. Thus, Hop/p60 and substrate proteins can form ternary complexes with hsc70. Hop/p60 exerts no effect on ATP and substrate binding but nevertheless interferes with protein refolding. Even though there is no direct interaction between these accessory proteins, Hap46 inhibits the binding of Hop/p60 to hsc70 but Hop/p60 does not inhibit the binding of Hap46 to hsc70. As judged from respective deletions, the amino-terminal portions of Hap46 and Hop/p60 are involved in this interference. These data suggest steric hindrance between Hap46 and Hop/p60 during interaction with distantly located binding sites on hsp70s. Thus, not only do the major domains of hsp70 chaperones communicate with each other, but cofactors interacting with these domains affect each other as well. 相似文献
108.
Zsofia Herbert Sandra Rauser Leslie Williams Neval Kapan Michaela Güntner Axel Walch George Boyan 《Journal of morphology》2010,271(12):1509-1526
The central complex is a major integrative region within the insect brain with demonstrated roles in spatial orientation, the regulation of locomotor behavior, and sound production. In the hemimetabolous grasshopper, the central complex comprises the protocerebral bridge, central body (CB), ellipsoid body, noduli, and accessory lobes, and this modular organization develops entirely during embryogenesis. From a biochemical perspective, a range of neuroactive substances has been demonstrated in these modules of the adult central complex, but little is known about their developmental expression. In this study, we use matrix‐assisted laser desorption/ionization‐imaging mass spectrometry on single brain slices to confirm the presence of several peptide families (tachykinin, allatostatin, periviscerokinin/pyrokinin, FLRFamide, and neuropeptide F) in the adult central complex and then use immunohistochemistry and histology to examine their developmental expression, together with that of the indolamin serotonin, and the endogenous messenger nitric oxide (NO; via its synthesizing enzyme). We find that each neuromodulator is expressed according to a unique, stereotypic, pattern within the various modules making up the central complex. Neuropeptides such as tachykinin (55%) and allatostatin (65%), and the NO‐synthesizing enzyme diaphorase (70%), are expressed earlier during embryonic development than the biogenic amine serotonin (80%), whereas periviscerokinin‐like peptides and FLRFamide‐like peptides begin to be expressed only postembryonically. Within the CB, these neuroactive substances are present in tangential projection neurons before they appear in columnar neurons. There is also no colocalization of serotonin‐positive and peptide‐positive projections up to the third larval instar during development, consistent with the clear dorsoventral layering of the neuropil we observe. Our results provide the first neurochemical fingerprint of the developing central complex in an hemimetabolous insect. J. Morphol., 2010. © 2010 Wiley‐Liss, Inc. 相似文献
109.
Timing of reproduction in a Darwin''s finch: temporal opportunism under spatial constraints 总被引:1,自引:0,他引:1
We investigated whether predation by the minor grison ( Galictis cuja , a small mustelid) played a key role in limiting a wild cavy population ( Cavia magna ), ultimately leading to its local extinction. Radio-telemetry and capture-mark-recapture techniques were used to estimate grison predation rates (kill rates), time-specific probabilities of apparent mortality (population loss rate), overall mortality and grison predation for the cavy population. Additionally, we present data on alternative prey species, grison diet and reproduction to show potential proximate mechanisms of grison predation on wild cavies. The predictions specified were mostly confirmed: (1) grison predation was responsible for almost 80% of the cavies killed by known predators; (2) grison predation probabilities paralleled those of overall mortality of cavies over time; and (3) also those of the apparent mortality of the population. Thus, the population dynamics and the local extinction of the cavy population were not due to emigration processes. (4) Grison predation rates were not density-dependent, but showed pronounced peaks during the austral summer. The grison mainly preyed on small mammals: two water-rat species and the wild cavies. When the availability of alternative prey decreased in summer, the grison appeared to specialise on cavies. The onset of grison reproduction was somewhat delayed in relation to the onset of cavy reproduction. The lack of alternative prey coincided with high grison food demands due to reproduction, leading to a very high predation pressure ultimately resulting in the local extinction of the cavy population. We conclude that grison predation was indeed the main factor driving changes of the cavy population studied and speculate why caviomorph rodents might be especially susceptible to local extinction processes. 相似文献
110.
Bis‐ and Tetrakis(carboxylato)platinum(IV) Complexes with Mixed Axial Ligands – Synthesis,Characterization, and Cytotoxicity
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Björn R. Hoffmeister Michaela Hejl Mahsa S. Adib‐Razavi Michael A. Jakupec Markus Galanski Bernhard K. Keppler 《化学与生物多样性》2015,12(4):559-574
A series of twelve novel diamminetetrakis(carboxylato)platinum(IV) and 18 novel bis(carboxylato)dichlorido(ethane‐1,2‐diamine)platinum(IV) complexes with mixed axial carboxylato ligands was synthesized and characterized by multinuclear 1H‐, 13C‐, 15N‐, and 195Pt‐NMR spectroscopy. Their cytotoxic potential was evaluated (by MTT assay) against three human cancer cell lines derived from ovarian teratocarcinoma (CH1/PA‐1), lung (A549), and colon carcinoma (SW480). In the cisplatin‐sensitive CH1/PA‐1 cancer cell line, diamminetetrakis(carboxylato)platinum(IV) complexes showed IC50 values in the low micromolar range, whereas, for the most lipophilic compounds of the bis(carboxylato)dichlorido(ethane‐1,2‐diamine)platinum(IV) series, IC50 values in the nanomolar range were found. 相似文献