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31.
Othman Al Musaimi Sophie V. Morse Lucia Lombardi Simona Serban Alessandra Basso Daryl R. Williams 《Journal of peptide science》2023,29(2):e3448
Successful manual synthesis of the TD2.2 peptide acting as a blood–brain barrier shuttle was achieved. TD2.2 was successfully synthesised by sequential condensation of four protected peptide fragments on solid-phase settings, after several unsuccessful attempts using the stepwise approach. These fragments were chosen to minimise the number of demanding amino acids (in terms of coupling, Fmoc removal) in each fragment that are expected to hamper the overall synthetic process. Thus, the hydrophobic amino acids as well as Arg(Pbf) were strategically spread over multiple fragments rather than having them congested in one fragment. This study shows how a peptide that shows big challenges in the synthesis using the common stepwise elongation methodology can be synthesised with an acceptable purity. It also emphasises that choosing the right fragment with certain amino acid constituents is key for a successful synthesis. It is worth highlighting that lower amounts of reagents were required to synthesise the final peptide with an identical purity to that obtained by the automatic synthesiser. 相似文献
32.
Fiorito Serena Collevecchio Chiara Epifano Francesco Genovese Salvatore Palumbo Lucia 《Phytochemistry Reviews》2023,22(1):73-84
Phytochemistry Reviews - Oxyprenylated secondary metabolites of plant, fungal, and microbial origin have emerged as biologically active natural compounds with a great potential for the next future.... 相似文献
33.
Matteo Zurlo Francesco Nicoli Davide Proietto Beatrice Dallan Cristina Zuccato Lucia Carmela Cosenza Jessica Gasparello Chiara Papi Elisabetta d'Aversa Monica Borgatti Chiara Scapoli Alessia Finotti Roberto Gambari 《Journal of cellular and molecular medicine》2023,27(3):353-364
Inhibitors of the mammalian target of rapamycin (mTOR) have been proposed to improve vaccine responses, especially in the elderly. Accordingly, testing mTOR inhibitors (such as Sirolimus) and other geroprotective drugs might be considered a key strategy to improve overall health resilience of aged populations. In this respect, Sirolimus (also known as rapamycin) is of great interest, in consideration of the fact that it is extensively used in routine therapy and in clinical studies for the treatment of several diseases. Recently, Sirolimus has been considered in laboratory and clinical studies aimed to find novel protocols for the therapy of hemoglobinopathies (e.g. β-Thalassemia). The objective of the present study was to analyse the activity of CD4+ and CD8+ T cells in β-Thalassemia patients treated with Sirolimus, taking advantages from the availability of cellular samples of the NCT03877809 clinical trial. The approach was to verify IFN-γ releases following stimulation of peripheral blood mononuclear cells (PBMCs) to stimulatory CEF and CEFTA peptide pools, stimulatory for CD4+ and CD8+ T cells, respectively. The main results of the present study are that treatment of β-Thalassemia patients with Sirolimus has a positive impact on the biological activity and number of memory CD4+ and CD8+ T cells releasing IFN-γ following stimulation with antigenic stimuli present in immunological memory. These data are to our knowledge novel and in our opinion of interest, in consideration of the fact that β-Thalassemia patients are considered prone to immune deficiency. 相似文献
34.
Pietro Cugini Loredana Di Palma Salvatore Di Simone Piernatale Lucia Paola Battisti Alessandro Coppola Giuseppe Leone 《Chronobiology international》1993,10(1):73-78
This study aimed to explore the 24-h patterns of stroke volume, cardiac output, and peripheral vascular resistance along with other correlated variables, such as left ventricular ejection time, ejection velocity index, thoracic fluid index, heart rate, and blood pressure. The study was performed on 12 clinically healthy subjects by means of a noninvasive beat-to-beat monitoring using the thoracic electric bioimpedance technique associated with the automated sphygmomano-metric recording. Time data series were analyzed by means of chronobiological procedures. The results documented the occurrence of a circadian rhythm for all the variables investigated, giving relevance to the beat-to-beat bioperiodicity of cardiac output and peripheral vascular resistance. Temporal quantification of the investigated variables may be useful for a better insight of the chronophysiology of the cardiovascular apparatus. 相似文献
35.
Lucia Pitzurra Manuela Puliti Mohamed Ali Burhan Fuad Francesco Bistoni Elisabetta Blasi 《FEMS immunology and medical microbiology》1993,7(4):289-295
Abstract The present study was designed to establish the susceptibility of macrophage-mediated effector functions to tetanus toxin (TT). Using the murine macrophage cell line, GG2EE, generated in vitro by v- raf /v- myc oncogenes, we have previously provided evidence that TT selectively inhibits interferon gamma (IFN-γ), but not basal, lysozyme activity. Here we show that while neither phagocytic nor candidacidal activities are affected by TT treatment, antitumoral activity is significantly impaired after exposure to TT. This phenomenon, which is dose-dependent, is fully ascribed to the holotoxin, as heat inactivated TT, C or A-B fragments result ineffective. Furthermore, C but not A-B fragment competes with TT in abrogating its inhibitory effects. Overall, these data indicate that TT is not a broad-spectrum, down-regulating signal on macrophage-mediated functions, thus implying that its toxic action is exerted on specific molecular targets. 相似文献
36.
Luca M. Neri Daniela Milani Marco Marchisio Lucia Bertolaso Fiorenzo Marinelli Francesco A. Manzoli Silvano Capitani 《Histochemistry and cell biology》1993,100(2):121-129
The rat pheochromocytoma PC12 cell line, which differentiates into sympathetic neurons under nerve growth factor (NGF) treatment, contains at least three phosphoinositidase C (PIC) isozymes, PIC , PIC , PIC . These isozymes have been previously shown to display a different subcellular localization. To determine whether or not NGF induces changes in the presence and/or distribution of PIC isozymes during PC12 neural differentiation, studies were carried out by means of in situ immunocytochemistry. After NGF administration the proliferative activity was progressively reduced to very low levels, as measured by bromodeoxyUridine incorporation, and a neuron-like morphology was displayed by almost all cells. In unstimulated PC12 cells, PIC was detected in the nucleus whereas PIC was only cytoplasmic; PIC was found in both cell compartments. In cells treated with NGF for 3 days, neural processes extended to twice the diameter of the cell body; the isoform was concentrated near the nucleus, while the immunoreactivity of the form remained constant and the form was increased. After 10 days of treatment with NGF, PIC was hardly detectable and PIC immunostaining was considerably decreased. On the contrary, PIC progressively increased and, after 14 days of NGF exposure, fully differentiated cells displayed an intense labelling of cell body and neurites. In the same cells, PIC and PIC were almost negative. These results suggest that NGF dependent neural differentiation is related to the selective down regulation of PIC and and the increase of PIC isozyme associated with the decrease of cell proliferation. 相似文献
37.
38.
L. Banci I. Bertini K. L. Bren M. A. Cremonini H. B. Gray C. Luchinat P. Turano 《Journal of biological inorganic chemistry》1996,1(2):117-126
The availability of NOE constraints and of the relative solution structure of a paramagnetic protein permits the use of pseudocontact
shifts as further structural constraints. We have developed a strategy based on: (1) determination of the χ tensor anisotropy
parameters from the starting structure; (2) recalculation of a new structure by using NOE and pseudocontact shift constraints simultaneously; (3) redetermination of the χ tensor anisotropy parameters from the new structure,
and so on until self-consistency. The system investigated is the cyanide derivative of a variant of the oxidized Saccharomyces cerevisiae iso-1-cytochrome c containing the Met80Ala mutation. The structure has been substantially refined. It is shown that the analysis of the deviation
of the experimental pseudocontact shifts from those calculated using the starting structure may be unsound, as may the simple
structure refinement based on the pseudocontact shift constraints only.
Received: 11 July 1995 / Accepted: 30 October 1995 相似文献
39.
Roberta Pierattelli Lucia Banci D. L. Turner 《Journal of biological inorganic chemistry》1996,1(4):320-329
The chemical shifts of several 13C nuclei positioned α to the haems in oxidised cyanide complexes of horseradish peroxidase and lignin peroxidase are reported and analysed in terms
of π molecular orbitals with perturbed D4h symmetry. The additional contributions to the paramagnetic shifts of 13C nuclei in the vinyl groups which arise from conjugation with the porphyrin π molecular orbitals are discussed, and an empirical correction factor is derived from a number of other compounds which contain
haems b. The orbital mixing parameter which is obtained from the analysis of the experimental 13C shifts is compared with the orientation of the axial histidine ligands in X-ray structures of related compounds and found
to be close to the orientation of the normal to the histidine ring. Comparison with the magnetic axes determined by fitting
the dipolar shifts of several protons which have been assigned previously also shows close agreement with the negative in-plane
rotation of the magnetic y axis. It is therefore possible to obtain the approximate orientation of the magnetic axes from 13C resonances of the haem and hence to determine the dipolar shifts at any point in space with respect to the haem by using
these axes together with the anisotropy of the magnetic susceptibility, which can be obtained by extrapolation from EPR g values. Excellent agreement is found between dipolar shifts obtained by fitting an empirical magnetic susceptibility tensor
and predictions based on 13C NMR and EPR in the case of lignin peroxidase. The agreement is less good in the case of horseradish peroxidase, in which
the empirical magnetic z axis appears to be tilted significantly away from the haem normal, though this may be due in part to the lack of accurate
atomic coordinates. It is concluded that useful estimates of the magnetic susceptibility tensor may be obtained from 13C NMR and EPR studies even in large mammalian peroxidases for which no structural models are available.
Received: 27 December 1995 / Accepted: 17 April 1996 相似文献
40.
Alberto M. Martelli Lucia Manzoli Silvia Rubbini Anna Maria Billi Renato Bareggi Lucio Cocco 《Biology of the cell / under the auspices of the European Cell Biology Organization》1995,83(1):15-22
Summary— Using two-dimensional polyacrylamide gels stained with Coomassie blue we have studied the protein composition of the nuclear matrix obtained from mouse erythroleukemic nuclei kept at O°C throughout the isolation procedure to prepare the high ionic strength resistant fraction (control matrix) or stabilized in vitro or in vivo by different procedures prior to subfractionation (ie 37°C incubation of isolated nuclei; sodium tetrathionate exposure of purified nuclei; heat shock of intact cells). When the matrix obtained from 37°C incubated nuclei was compared with the control matrix, striking differences in the polypeptide pattern were seen if the protein was obtained in both cases from an equivalent number of nuclei. On the other hand, if the same amount of protein for both the samples was applied to the gels the differences were less evident. Sodium tetrathionate stabilization of isolated nuclei and heat shock of intact cells produced a matrix protein pattern that was very similar and differed from that of the in vitro heat-exposed matrix. Using specific polyclonal antisera, we demonstrate that nucleolar proteins B23/numatrin and C23/nucleolin were very abundant in the matrix obtained from chemically-treated nuclei or in vivo heat-stabilized nuclei but were recovered in very small amounts (B23) or completely absent (C23) in the matrix prepared from nuclei heated to 37°C in vitro. Differences were seen also in the recovery of nuclear lamins, and especially lamin B, that was poorly represented in the sodium tetrathionate-stabilized matrix. The results demonstrate that in mouse erythroleukemia cells the increased recovery of nuclear matrix protein that is seen after in vitro heating of isolated nuclei is predominantly due to an additional recovery of the same types of polypeptides that are detected also in the absence of such a treatment. The data also indicate that in vivo heat shock of intact cells produces a nuclear matrix protein pattern that is more similar to the pattern seen after stabilization of purified nuclei with sodium tetrathionate and differs significantly from that obtained by exposing nuclei to 37°C in vitro, unlike to that what previous reports have indicated. 相似文献