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231.
232.
Maria Luisa Balestrieri Alfonso Giovane Lara Milone Francesca Felice Carmela Fiorito Valeria Crudele Annaclaudia Esposito Raffaele Rossiello Pellegrino Biagio Minucci Bartolomeo Farzati Luigi Servillo Claudio Napoli 《Journal of biochemical and molecular toxicology》2010,24(6):351-360
Exposure of human endothelial progenitor cells (EPCs) to tumor necrosis factor‐α (TNF‐α) reduced their number and biological activity. Yet, signal transduction events linked to TNF‐α action are still poorly understood. To address this issue, we examined the possible effect of fasudil and Y27632, two inhibitors of Rho kinase pathway, which is involved in endothelial dysfunction, atherosclerosis, and in‐ flammation. Results demonstrated that incubation with fasudil starting from 50 μM but not Y27632 determined a dose‐dependent improvement of EPC number during exposure to TNF‐α (P < 0.05 vs. TNF‐α alone). Analysis of the signal transduction pathway activated by TNF‐α revealed that the increased expression of p‐p38 was not significantly altered by fasudil. Instead, fasudil blocked the TNF‐α induced phosphorylation of Erk1/2 (P < 0.05 vs. TNF‐α) as well as the inhibitor of Erk1/2‐specific phosphorylated form, i.e., PD98059 (P < 0.05 vs. TNF‐α). These results were confirmed by analysis of these kinases by confocal microscopy. Finally, 2D‐DIGE and MALDI‐TOF/TOF analysis of EPCs treated with fasudil revealed increased expression levels of an actin‐related protein and an adenylyl cyclase associated protein and decreased expression levels of proteins related to radical scavenger and nucleotide metabolism. These findings suggest that fasudil positively affects EPC number and that other major signals might take part to this complex pathway. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:351–360, 2010; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20345 相似文献
233.
De Rossi A Zanchetta M Vitone F Antonelli G Bagnarelli P Buonaguro L Capobianchi MR Clementi M Abbate I Canducci F Monachetti A Riva E Rozera G Scagnolari C Tagliamonte M Re MC;SIVIM 《The new microbiologica》2010,33(4):293-302
Despite the widespread use of molecular biology techniques, standardized methods for the measurement of HIV-1 proviral DNA are currently lacking and several discordant results are still present in different studies. To assess the clinical meaning of the proviral DNA load, a study group comprising seven different laboratories was set up to standardize a HIV-1 proviral DNA quantification method able to assess the DNA proviral load of the most relevant circulating HIV-1 subtypes. Reference samples (24 cellular samples infected with HIV-1 clade B, and 40 samples of peripheral blood mononuclear cells containing different concentrations of plasmids expressing different HIV-1 clades) were distributed and tested blindly. All laboratories employed hTERT gene as housekeeping gene and primers within the gag gene to quantify different HIV-1 clades. Inter-laboratory results did not differ statistically but showed only minor variations concerning HIV-1 DNA amounts and different HIV clades, with a good agreement among the laboratories participating in the study. Since test standardization represents a key step for future application in clinical practice, further studies of the patients' samples are in progress to establish the real meaning and utility of the proviral DNA load for clinical management of HIV-1 infected patients. 相似文献
234.
Romualdo Caputo Marina DellaGreca Ivan de Paola Domenico Mastroianni Luigi Longobardo 《Amino acids》2010,38(1):305-310
The synthesis of new substituted prolines carrying at C-4 a second α-amino acid residue is reported. The amino acid, l-cysteine or l-selenocysteine, is linked to the proline ring through the sulfur or the selenium atom, respectively. The products were prepared
with different stereochemistry at C-4, in few and clean high-yielding steps, with suitable protections for solid phase applications.
The introduction of both sulfur and selenium atoms at C-4 of the proline ring seems to enhance significantly the cis geometry
at the prolyl amide bond. 相似文献
235.
Federica Susta Davide Chiasserini Katia Fettucciari Pier Luigi Orvietani Flavia Quotadamo Rosina Noce Andrea Bartoli Pierfrancesco Marconi Lanfranco Corazzi Luciano Binaglia 《Proteomics》2010,10(11):2099-2112
Protein expression changes induced in thioglycolate‐elicited peritoneal murine macrophages (MΦ) by infection with type III Group B Streptococcus (GBS) are described. Proteins from control MΦ and MΦ incubated 2 h with live or heat‐inactivated GBS were separated by 2‐DE. Proteins whose expression was significantly different in infected MΦ, as compared with control cells, were identified by MS/MS analysis. Changes in the expression level of proteins involved in both positive and negative modulation of phagocytic functions, stress response and cell death were induced in MΦ by GBS infection. In particular, expression of enzymes playing a key role in production of reactive oxygen species was lowered in GBS‐infected MΦ. Significant alterations in the expression of some metabolic enzymes were also observed, most of the glycolytic and of the pentose‐cycle enzymes being down‐regulated in MΦ infected with live GBS. Finally, evidence was obtained that GBS infection affects the expression of enzymes or enzyme subunits involved in ATP synthesis and in adenine nucleotides interconversion processes. 相似文献
236.
A global approach to crop wild relative conservation: securing the gene pool for food and agriculture 总被引:1,自引:0,他引:1
Nigel Maxted Shelagh Kell Álvaro Toledo Ehsan Dulloo Vernon Heywood Toby Hodgkin Danny Hunter Luigi Guarino Andy Jarvis Brian Ford-Lloyd 《Kew Bulletin》2010,65(4):561-576
In light of the growing concern over the potentially devastating impacts on biodiversity and food security of climate change
and the massively growing world population, taking action to conserve crop wild relatives (CWR), is no longer an option —
it is a priority. Crop wild relatives are species closely related to crops, including their progenitors, many of which have
the potential to contribute beneficial traits to crops, such as pest or disease resistance, yield improvement or stability.
They are a critical component of plant genetic resources for food and agriculture (PGRFA), have already made major contributions
to crop production and are vital for future food security; their systematic conservation in ways that ensure their continuing
availability for use is therefore imperative. This is a complex, interdisciplinary, global issue that has been addressed by
various national and international initiatives. Drawing on the lessons learnt from these initiatives we can now propose a
global approach to CWR conservation, the key elements of which are: (1) estimating global CWR numbers, (2) assessment of the
global importance of CWR diversity, (3) current conservation status, (4) threats to CWR diversity, (5) systematic approaches
to CWR conservation, (6) CWR informatics, and (7) enhancing the use of CWR diversity. 相似文献
237.
Oana A. Cuzman Stefano Ventura Claudio Sili Cristina Mascalchi Tulio Turchetti Luigi P. D’Acqui Piero Tiano 《Microbial ecology》2010,60(1):81-95
Among the stone monumental assets, artistic fountains are particularly affected by microbial colonization due to constant
contact with water, giving rise to biodegradation processes related with physical–chemical and aesthetical alterations. In
this paper, we make an overview of reported biodiversity of the phototrophic patina developed in various fountains of Italy
and Spain. The microbial composition of four fountains (two from Florence, Italy and two from Granada, Spain) was investigated
using traditional and/or molecular techniques. The results indicated many common similarities with regard the phototrophic
biodiversity for all the investigated fountains. Automated ribosomal RNA intergenic spacer analysis (ARISA), a molecular fingerprint
tool, was used to examine the eubacterial and cyanobacterial community for two of the investigated fountains. The principal
component analysis of ARISA profiles strengthens the results obtained by traditional methods and revealed separate clusters,
as a consequence of the differences of micro-environmental conditions for each fountain. 相似文献
238.
Borroto-Escuela DO Romero-Fernandez W Tarakanov AO Marcellino D Ciruela F Agnati LF Fuxe K 《Biochemical and biophysical research communications》2010,401(4):605-610
In view of the co-distribution of dopamine D2LR and 5-hydroxytryptamine 5-HT2A receptors (D2LR and 5-HT2AR, respectively) within inter alia regions of the dorsal and ventral striatum and their role as a target of antipsychotic drugs; in this study we assessed the potential existence of D2LR-5-HT2AR heteromers in living cells and the functional consequences of this interaction. Thus, by means of a proximity-based bioluminescence resonance energy transfer (BRET) approach we demonstrated that the D2LR and the 5-HT2AR form stable and specific heteromers when expressed in HEK293T mammalian cells. Furthermore, when the D2LR-5-HT2AR heteromeric signaling was analyzed we found that the 5-HT2AR-mediated phospholipase C (PLC) activation was synergistically enhanced by the concomitant activation of the D2LR as shown in a NFAT-luciferase reporter gene assay and a specific and significant rise of the intracellular calcium levels were observed when both receptors were simultaneously activated. Conversely, when the D2LR-mediated adenylyl cyclase (AC) inhibition was assayed we showed that costimulation of D2LR and 5-HT2AR within the heteromer led to inhibition of the D2LR functioning, thus suggesting the existence of a 5-HT2AR-mediated D2LR trans-inhibition phenomenon. Finally, a bioinformatics study reveals that the triplet amino acid homologies LLT (Leu-Leu-Thr) and AIS (Ala-Ile-Ser) in TM1 and TM3, respectively of the D2R-5-HT2AR may be involved in the receptor interface. Overall, the presence of the D2LR-5-HT2AR heteromer in discrete brain regions is postulated based on the existence of D2LR-5-HT2A receptor-receptor interactions in living cells and their codistribution inter alia in striatal regions. Possible novel therapeutic strategies for treatment of schizophrenia should be explored by targeting this heteromer. 相似文献
239.
Stanzione F Esposito L Paladino A Pedone C Morelli G Vitagliano L 《Biophysical journal》2010,99(7):2273-2278
Neurotrophins (NTs) represent a family of proteins that play an important role in the survival, development, and function of neurons. Extensive efforts are currently being made to develop small molecules endowed with agonist or antagonist NT activity. The structurally versatile N-termini of these proteins are considered regions of interest for the design of new molecules. By combining experimental and computational approaches, we analyzed the intrinsic conformational preferences of the N-termini of two of the most important NTs: NGF (NGF-Nter) and NT4 (NT4-Nter). Circular dichroism spectra clearly indicate that both peptides show a preference for random coil states. Because this finding does not preclude the possibility that structured forms may occur in solution as minor conformational states, we performed molecular-dynamics simulations to gain insights into the structural features of populated species. In line with the circular dichroism analysis, the simulations show a preference for unstructured states for both peptides. However, the simulations also show that for NT4-Nter, and to a lesser extent for NGF-Nter, helical conformations, which are required for binding to the Trk receptor, are present in the repertoire of structures that are intrinsically accessible to these peptides. Accordingly, molecular recognition of NTs by the Trk receptor is accomplished by the general mechanism known as population shift. These findings provide a structural rationale for the observed activity of synthetic peptides based on these NT regions. They also suggest strategies for the development of biologically active peptide-based compounds. 相似文献
240.
Valentina Ruggieri Giovanni Vitale Monica Filaferro Claudio Frigeri Luigi A. Pini Maurizio Sandrini 《Life sciences》2010,86(13-14):510-517
AimsCombinations of non-steroidal anti-inflammatory drugs (NSAIDs) and cannabinoids are promising because of their potential synergistic effects in analgesia, resulting in a reduction in dosage and minimizing adverse reactions. The analgesic effect of acetylsalicylic acid (ASA), probably due to a central mechanism, also implicates changes in the central monoaminergic system. Therefore, we decided to evaluate the antinociceptive interaction between the CB1 receptor agonist, HU210, and ASA in tests involving central pain in rats as well as the implication of the central serotonergic system thereon.Main methodsThe selective CB1 antagonist SR141716A and the potent cannabinoid agonist HU210 were evaluated alone and in combination with ASA in both algesimetric tests (hot-plate and formalin tests) and for 5-HT activity and 5-HT2 receptor density and affinity.Key findingsASA or HU210 alone showed a dose-dependent effect in both tests. HU210, at an inactive dose, significantly increased the antinociceptive effect of the sub-active dose of ASA. SR141716A (1.5 mg/kg i.p.) was ineffective per se and failed to modify antinociception induced by the HU210 plus ASA combination in either test. HU210 plus ASA significantly decreased the 5-HIAA/5-HT ratio and the 5-HT2 receptor density in the frontal cortex, changes not antagonized by SR141716A.SignificanceThe present study provides evidence that mutual potentiation of the antinociceptive effects of HU210 and ASA may, at least partly, depend on serotonergic mechanisms, with an indirect participation of cannabinodiergic mechanism. In conclusion, combinations of low doses of cannabinoids and NSAIDs may be of interest from the therapeutic point of view. 相似文献