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991.
Marrari A Iero M Pilla L Villa S Salvioni R Valdagni R Parmiani G Rivoltini L 《Cancer immunology, immunotherapy : CII》2007,56(4):429-445
Radical prostatectomy and radiation therapy provide excellent localized prostate cancer (PC) control. Although the majority
of prostate carcinoma is nowadays diagnosed at early stages with favourable risk features, in patients up to 30–40% it recurs
within 10 years. Furthermore, the lack of effective therapies, once prostate carcinoma becomes refractory to androgen deprivation,
mandates the development of alternative therapeutic options. There is a growing interest in harnessing the potency and specificity
of anti-tumour immunity through the generation of fully competent dendritic cells and tumour reactive effector lymphocytes.
Several strategies to treat or prevent the development of metastatic PC have been explored in clinical trials and are summarized
in this review, considering also the feasibility and safety of these approaches. In some cases clinical responses were achieved
showing that vaccine-primed T cells induced anti-tumour activity in vivo. The present findings and perspectives of the immunologic
interventions in PC patients will be discussed. 相似文献
992.
Ion currents and cytosolic free calcium ([Ca(2+)](i)) elevations are crucial events in triggering the complex machinery involved in both gamete maturation and fertilization. Oocyte maturation is triggered by hormone signaling which causes ion currents and [Ca(2+)](i) increase. Extracellular calcium seems to be required for meiosis progression since: (i) calcium depletion in the maturation medium severely affects oocyte developmental competence; (ii) the activity of plasma membrane L-type Ca(2+) currents decreases during maturation; (iii) the exposure to verapamil, a specific Ca(2+) channel blocker, decreases in vitro maturation efficiency. In spermatozoa, maturation initiates inside the epididymis and ends in the female genital tract. During their journey through the female reproductive tract, sperm undergo a dramatic selection and capacitation achieving fertilization competence. Adhesion to the tubal epithelium extends sperm life through depression of [Ca(2+)](i) until capacitation signals trigger an [Ca(2+)](i) elevation followed by sperm release. At fertilization, egg-sperm interaction evokes well-described transient and almost simultaneous events: i.e., fertilization current, a change in resting potential, and an increase in free [Ca(2+)](i) concentration. These events, termed oocyte activation, are the direct consequence of sperm interaction via either activation of a receptor or entry of a sperm factor. The latter hypothesis has been recently supported by the discovery of PCLzeta, a sperm-specific isozyme triggering a dramatic [Ca(2+)](i) increase via inositol 1,4,5-trisphosphate (IP(3)) production. The course of ion currents and [Ca(2+)](i) transients during maturation and fertilization plays a pivotal role in correct embryo development. 相似文献
993.
Cinquegrani Gloria Spigoni Valentina Iannozzi Nicolas Thomas Parello Vanessa Bonadonna Riccardo C. Dei Cas Alessandra 《Cell biology and toxicology》2022,38(4):667-678
Cell Biology and Toxicology - The inflammatory potential of SARS-CoV-2 Spike S1 (Spike) has never been tested in human primary macrophages (MΦ). Different recombinant Spikes might display... 相似文献
994.
Riccardo Porcari Christos Proukakis Christopher A. Waudby Benedetta Bolognesi P. Patrizia Mangione Jack F. S. Paton Stephen Mullin Lisa D. Cabrita Amanda Penco Annalisa Relini Guglielmo Verona Michele Vendruscolo Monica Stoppini Gian Gaetano Tartaglia Carlo Camilloni John Christodoulou Anthony H. V. Schapira Vittorio Bellotti 《The Journal of biological chemistry》2015,290(4):2395-2404
The conversion of α-synuclein from its intrinsically disordered monomeric state into the fibrillar cross-β aggregates characteristically present in Lewy bodies is largely unknown. The investigation of α-synuclein variants causative of familial forms of Parkinson disease can provide unique insights into the conditions that promote or inhibit aggregate formation. It has been shown recently that a newly identified pathogenic mutation of α-synuclein, H50Q, aggregates faster than the wild-type. We investigate here its aggregation propensity by using a sequence-based prediction algorithm, NMR chemical shift analysis of secondary structure populations in the monomeric state, and determination of thermodynamic stability of the fibrils. Our data show that the H50Q mutation induces only a small increment in polyproline II structure around the site of the mutation and a slight increase in the overall aggregation propensity. We also find, however, that the H50Q mutation strongly stabilizes α-synuclein fibrils by 5.0 ± 1.0 kJ mol−1, thus increasing the supersaturation of monomeric α-synuclein within the cell, and strongly favors its aggregation process. We further show that wild-type α-synuclein can decelerate the aggregation kinetics of the H50Q variant in a dose-dependent manner when coaggregating with it. These last findings suggest that the precise balance of α-synuclein synthesized from the wild-type and mutant alleles may influence the natural history and heterogeneous clinical phenotype of Parkinson disease. 相似文献
995.
996.
Francesco Lucertini Elisa Ponzio Michael Di Palma Claudia Galati Ario Federici Pamela Barbadoro Marcello M. D’Errico Emilia Prospero Patrizia Ambrogini Riccardo Cuppini Davide Lattanzi Andrea Minelli 《PloS one》2015,10(11)
Physical fitness has salutary psychological and physical effects in older adults by promoting neuroplasticity and adaptation to stress. In aging, however, the effects of fitness on the hypothalamic-pituitary-adrenal (HPA) axis are mixed. We investigated the association between cardiorespiratory fitness and HPA activity in healthy elderly men (n = 22, mean age 68 y; smokers, obese subjects, those taking drugs or reporting recent stressful events were excluded), by measuring in saliva: i) daily pattern of cortisol secretion (6 samples: 30’ post-awakening, and at 12.00, 15.00, 18.00, 21.00, 24.00 h); and ii) the cortisol response to a mental challenge. Cardiorespiratory fitness (VO2max) was estimated using the Rockport Walking Test and the participants were assigned to high-fit (HF, ≥60°, n = 10) and low-fit (LF, ≤35°, n = 12) groups according to age-specific percentiles of VO2max distribution in the general population. At all daytimes, basal cortisol levels were lower in the HF than the LF group, most notably in the evening and midnight samples, with a significant main effect of physical fitness for cortisol levels overall; the area-under-the-curve for total daily cortisol output was significantly smaller in the HF group. Among the subjects who responded to mental stress (baseline-to-peak increment >1.5 nmol/L; n = 13, 5 LF, 8 HF), the amplitude of cortisol response and the steepness of recovery decline displayed an increasing trend in the HF subjects, although between-group differences failed to reach the threshold for significance. In conclusion, cardiorespiratory fitness in healthy aging men is negatively correlated with daily cortisol output and contributes to buffering the HPA dysregulation that occurs with advancing age, thus possibly playing a beneficial role in contrasting age-related cognitive and physical decline. 相似文献
997.
998.
Teja Tscharntke Riccardo Bommarco Yann Clough Thomas O. Crist David Kleijn Tatyana A. Rand Jason M. Tylianakis Saskya van Nouhuys Stefan Vidal 《Biological Control》2007,43(3):294-309
Conservation biological control in agroecosystems requires a landscape management perspective, because most arthropod species experience their habitat at spatial scales beyond the plot level, and there is spillover of natural enemies across the crop–noncrop interface. The species pool in the surrounding landscape and the distance of crop from natural habitat are important for the conservation of enemy diversity and, in particular, the conservation of poorly-dispersing and specialized enemies. Hence, structurally complex landscapes with high habitat connectivity may enhance the probability of pest regulation. In contrast, generalist and highly vagile enemies may even profit from the high primary productivity of crops at a landscape scale and their abundance may partly compensate for losses in enemy diversity. Conservation biological control also needs a multitrophic perspective. For example, entomopathogenic fungi, plant pathogens and endophytes as well as below- and above-ground microorganisms are known to influence pest-enemy interactions in ways that vary across spatiotemporal scales. Enemy distribution in agricultural landscapes is determined by beta diversity among patches. The diversity needed for conservation biological control may occur where patch heterogeneity at larger spatial scales is high. However, enemy communities in managed systems are more similar across space and time than those in natural systems, emphasizing the importance of natural habitat for a spillover of diverse enemies. According to the insurance hypothesis, species richness can buffer against spatiotemporal disturbances, thereby insuring functioning in changing environments. Seemingly redundant enemy species may become important under global change. Complex landscapes characterized by highly connected crop–noncrop mosaics may be best for long-term conservation biological control and sustainable crop production, but experimental evidence for detailed recommendations to design the composition and configuration of agricultural landscapes that maintain a diversity of generalist and specialist natural enemies is still needed. 相似文献
999.
1000.
Bondanza S Maurelli R Paterna P Migliore E Giacomo FD Primavera G Paionni E Dellambra E Guerra L 《Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society》2007,20(4):288-300
Vitiligo depigmentation is considered a consequence of either melanocyte disappearance or loss of functioning melanocytes in the involved areas. However, it has been reported that keratinocytes in involved vitiligo skin are damaged too. Based on this evidence, we evaluated the in vitro behaviour, in life span cultures, of involved and uninvolved vitiligo keratinocytes and their expression of proliferation, differentiation and senescence markers. An additional purpose was to investigate whether vitiligo keratinocytes from depigmented skin are able to sustain survival and growth of normal melanocytes (when added in co-culture experiments), as normal human keratinocytes manage to do. Our results demonstrate that almost all involved vitiligo keratinocytes have a shorter life span in vitro than the uninvolved cells and all of them do not maintain melanocytes in culture in a physiological ratio. Modification of proliferation and senescence marker expression also occurs. Indeed, we detected low initial expression levels of the senescence marker p16 in involved vitiligo keratinocytes, despite their shorter in vitro life span, and increased expression of proliferating cell nuclear antigen and p53. This preliminary analysis of a small number of in vitro cultured vitiligo keratinocytes suggests an impaired senescence process in lesional vitiligo keratinocytes and attempts to regulate it. 相似文献