全文获取类型
收费全文 | 3280篇 |
免费 | 225篇 |
国内免费 | 3篇 |
出版年
2023年 | 21篇 |
2022年 | 32篇 |
2021年 | 67篇 |
2020年 | 30篇 |
2019年 | 52篇 |
2018年 | 58篇 |
2017年 | 55篇 |
2016年 | 119篇 |
2015年 | 181篇 |
2014年 | 198篇 |
2013年 | 241篇 |
2012年 | 304篇 |
2011年 | 264篇 |
2010年 | 131篇 |
2009年 | 119篇 |
2008年 | 195篇 |
2007年 | 215篇 |
2006年 | 169篇 |
2005年 | 166篇 |
2004年 | 142篇 |
2003年 | 128篇 |
2002年 | 122篇 |
2001年 | 36篇 |
2000年 | 28篇 |
1999年 | 33篇 |
1998年 | 23篇 |
1997年 | 24篇 |
1996年 | 25篇 |
1995年 | 22篇 |
1994年 | 19篇 |
1993年 | 24篇 |
1992年 | 21篇 |
1991年 | 14篇 |
1990年 | 10篇 |
1989年 | 16篇 |
1988年 | 17篇 |
1987年 | 8篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 19篇 |
1983年 | 10篇 |
1982年 | 17篇 |
1981年 | 8篇 |
1979年 | 12篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1974年 | 14篇 |
1971年 | 6篇 |
1964年 | 6篇 |
1952年 | 4篇 |
排序方式: 共有3508条查询结果,搜索用时 31 毫秒
91.
Vera Jankowski Markus T?lle Thi Nguyet Anh Tran Markus van der Giet Mirjam Schuchardt Kerstin Lehmann Doreen Janke Burkhard Flick Alberto Arduan Ortiz Ni?o Maria Dolores Sanchez Martin Tepel Walter Zidek Joachim Jankowski 《PloS one》2013,8(7)
The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U) from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up4U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up4U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up4U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up4U after stimulation with shear stress. Mean total plasma Up4U concentrations of healthy subjects (N = 6) were sufficient to induce angiogenic and proliferative effects (1.34±0.26 nmol L-1). In conclusion, Up4U is a novel strong human endothelium-derived angiogenic factor. 相似文献
92.
Wanda M. Admiraal Everlina M. Vlaar Vera Nierkens Frits Holleman Barend J. C. Middelkoop Karien Stronks Irene G. M. van Valkengoed 《PloS one》2013,8(7)
Aim
To study 1-year effectiveness of an intensive, culturally targeted lifestyle intervention in general practice for weight status and metabolic profile of South-Asians at risk of type 2 diabetes.Methods
536 South-Asians at risk of type 2 diabetes were randomized to an intervention (n = 283) or control (n = 253) group. The intervention, which was targeted culturally to the South-Asian population, consisted of individual lifestyle counselling, a family session, cooking classes, and supervised physical activity programme. All components of the intervention were carried out by professionals as part of their daily clinical practice. The control group received generic lifestyle advice. Change in weight status and metabolic profile were assessed after 1 year.Results
After 1 year, 201 participants were lost to follow-up. Remaining participants in intervention (n = 177) and control (n = 158) group had similar baseline characteristics. Weight loss in the intervention group was 0.2±3.3 kg, weight gain in the control group was 0.4±3.1 kg (p = 0.08). Changes in other weight-related measurements did not differ significantly between groups. Furthermore, there were no differences between groups in changes of metabolic profile. All results remained similar after repeating analyses in a multiple imputed dataset.Discussion
An intensive, culturally targeted, lifestyle intervention of 1 year did not improve weight status and metabolic profile of South-Asians at risk of type 2 diabetes. The laborious recruitment, high drop-out, and lack of effectiveness emphasise the difficulty of realising health benefits in practice and suggest that this strategy might not be the optimal approach for this population.Trial Registration
Nederlands Trial Register NTR1499 相似文献93.
Human Hemorrhagic Pulmonary Leptospirosis: Pathological Findings and Pathophysiological Correlations
Thales De Brito Vera Demarchi Aiello Luis Fernando Ferraz da Silva Ana Maria Gon?alves da Silva Wellington Luiz Ferreira da Silva Jussara Bianchi Castelli Antonio Carlos Seguro 《PloS one》2013,8(8)
Background
Leptospirosis is a re-emerging zoonosis with protean clinical manifestations. Recently, the importance of pulmonary hemorrhage as a lethal complication of this disease has been recognized. In the present study, five human necropsies of leptospirosis (Weil‘s syndrome) with extensive pulmonary manifestations were analysed, and the antibodies expressed in blood vessels and cells involved in ion and water transport were used, seeking to better understand the pathophysiology of the lung injury associated with this disease.Principal Findings
Prominent vascular damage was present in the lung microcirculation, with decreased CD34 and preserved aquaporin 1 expression. At the periphery and even inside the extensive areas of edema and intraalveolar hemorrhage, enlarged, apparently hypertrophic type I pneumocytes (PI) were detected and interpreted as a non-specific attempt of clearence of the intraalveolar fluid, in which ionic transport, particularly of sodium, plays a predominant role, as suggested by the apparently increased ENaC and aquaporin 5 expression. Connexin 43 was present in most pneumocytes, and in the cytoplasm of the more preserved endothelial cells. The number of type II pneumocytes (PII) was slightly decreased when compared to normal lungs and those of patients with septicemia from other causes, a fact that may contribute to the progressively low PI count, resulting in deficient restoration after damage to the alveolar epithelial integrity and, consequently, a poor outcome of the pulmonary edema and hemorrhage.Conclusions
Pathogenesis of lung injury in human leptospirosis was discussed, and the possibility of primary non-inflammatory vascular damage was considered, so far of undefinite etiopathogenesis, as the initial pathological manifestation of the disease. 相似文献94.
Leiz M. C. Véras Vanessa R. R. Cunha Filipe C. D. A. Lima Maria A. Guimar?es Marianne M. Vieira Yuri D. M. Campelo Vanessa Y. Sakai David F. Lima Paulo S. Carvalho Jr Javier A. Ellena Paulo R. P. Silva Luciene C. Vasconcelos Markus Godejohann Helena M. Petrilli Vera R. L. Constantino Yvonne P. Mascarenhas José Roberto de Souza de Almeida Leite 《PloS one》2013,8(6)
This paper presents an industrial scale process for extraction, purification, and isolation of epiisopiloturine (EPI) (2(3H)-Furanone,dihydro-3-(hydroxyphenylmethyl)-4-[(1-methyl-1H-imidazol-4-yl)methyl]-, [3S-[3a(R*),4b]]), which is an alkaloid from jaborandi leaves (Pilocarpus microphyllus Stapf). Additionally for the first time a set of structural and spectroscopic techniques were used to characterize this alkaloid. EPI has shown schistomicidal activity against adults and young forms, as well as the reduction of the egg laying adult worms and low toxicity to mammalian cells (in vitro). At first, the extraction of EPI was done with toluene and methylene chloride to obtain a solution that was alkalinized with ammonium carbonate. The remaining solution was treated in sequence by acidification, filtration and alkalinization. These industrial procedures are necessary in order to remove impurities and subsequent application of the high performance liquid chromatography (HPLC). The HPLC was employed also to remove other alkaloids, to obtain EPI purity higher than 98%. The viability of the method was confirmed through HPLC and electrospray mass spectrometry, that yielded a pseudo molecular ion of m/z equal to 287.1 Da. EPI structure was characterized by single crystal X-ray diffraction (XRD), 1H and 13C nuclear magnetic resonance (NMR) in deuterated methanol/chloroform solution, vibrational spectroscopy and mass coupled thermal analyses. EPI molecule presents a parallel alignment of the benzene and the methyl imidazol ring separated by an interplanar spacing of 3.758 Å indicating a π-π bond interaction. The imidazole alkaloid melts at 225°C and decomposes above 230°C under air. EPI structure was used in theoretical Density Functional Theory calculations, considering the single crystal XRD data in order to simulate the NMR, infrared and Raman spectra of the molecule, and performs the signals attribution. 相似文献
95.
Hllriegl Vera Barkleit Astrid Spielmann Vladimir Li Wei Bo 《Radiation and environmental biophysics》2020,59(1):121-130
Radiation and Environmental Biophysics - Double tracer studies in healthy human volunteers with stable isotopes of cerium citrate were performed with the aim of investigating the gastro-intestinal... 相似文献
96.
97.
N. Belén Rumie Vittar María Julia Lamberti María Florencia Pansa Renzo E. Vera M. Exequiel RodriguezI. Sol Cogno Laura N. Milla SanabriaViviana A. Rivarola 《生物化学与生物物理学报:癌评论》2013
As with natural ecosystems, species within the tumor microenvironment are connected by pairwise interactions (e.g. mutualism, predation) leading to a strong interdependence of different populations on each other. In this review we have identified the ecological roles played by each non-neoplastic population (macrophages, endothelial cells, fibroblasts) and other abiotic components (oxygen, extracellular matrix) directly involved with neoplastic development. A way to alter an ecosystem is to affect other species within the environment that are supporting the growth and survival of the species of interest, here the tumor cells; thus, some features of ecological systems could be exploited for cancer therapy. We propose a well-known antitumor therapy called photodynamic therapy (PDT) as a novel modulator of ecological interactions. We refer to this as “ecological photodynamic therapy.” The main goal of this new strategy is the improvement of therapeutic efficiency through the disruption of ecological networks with the aim of destroying the tumor ecosystem. It is therefore necessary to identify those interactions from which tumor cells get benefit and those by which it is impaired, and then design multitargeted combined photodynamic regimes in order to orchestrate non-neoplastic populations against their neoplastic counterpart. Thus, conceiving the tumor as an ecological system opens avenues for novel approaches on treatment strategies. 相似文献
98.
Susanne Schwarze Horst Bleckmann Vera Schluessel 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2013,199(10):843-856
Animals face different threats; to survive, they have to anticipate how to react or how to avoid these. It has already been shown in teleosts that selected regions in the telencephalon, i.e., the medial pallium, are involved in avoidance learning strategies. No such study exists for any chondrichthyan. In nature, an avoidance reaction may vary, ranging from a ‘freeze’ reaction to a startling response and quick escape. This study investigated whether elasmobranchs (Chiloscyllium griseum and C. punctatum) can be conditioned in an aversive classical conditioning paradigm. Upon successful conditioning, the dorsal, medial and lateral pallium were removed (group 1) and performance tested again. In a second group, the same operation was performed prior to training. While conditioning was successful in individuals of both groups, no escape responses were observed. Post-operative performance was assessed and compared between individual and groups to reveal if the neural substrates governing avoidance behavior or tasks learned in a classical conditioning paradigm are located within the telencephalon, as has been shown for teleosts such as goldfish. 相似文献
99.
German Andres Estrada Vera Lúcia Divan Baldani Danilo Messias de Oliveira Segundo Urquiaga José Ivo Baldani 《Plant and Soil》2013,369(1-2):115-129
Background and Aims
Plant growth-promoting bacteria, mainly diazotrophs and phosphate solubilizers, can reduce the use of chemical fertilizers for rice crops. Here, diazotrophic bacteria isolated from rice were screened for their ability to solubilize inorganic P (Pi) in vitro and in association with rice plants cultivated in pots.Methods
Forty-nine isolates were tested for the ability to solubilize Pi on NBRIP and GL agar plate media and seven selected strains were further evaluated in NBRIP liquid medium. Three of these strains were inoculated in rice plants grown in soil pots containing 15N-labeled fertilizer and two sources of P: tricalcium phosphate (TCP) or simple superphosphate (SSP). The dry matter, yield, N, P, and the 15N content accumulated in plant tissues were measured at 135 days after planting.Results
Seven strains belonging to the genera Herbaspirillum and Burkholderia formed a halo of solubilized Pi on agar plates. The Burkholderia strains showed peak soluble P (around 200 mg P L?1) on the fifth day when grown in NBRIP liquid medium for 14 days. Inoculation of Herbaspirillum strains (H18, ZA15) and a Burkholderia vietaminensis strain (AR114) increased rice grain yield from 33 to 47 % with TCP and 18 to 44 % with TSS, respectively. The bacterial inoculation led to enhanced N-use efficiency of the 15N-labeled fertilizer.Conclusion
These results suggest that the selection and use of P-solubilizing diazotrophic bacteria are a good strategy to promote P solubilization and/or N use efficiency in rice plants. 相似文献100.
Abnormal mechanical loading may trigger cartilage degeneration associated with osteoarthritis. Tissue response to load has been the subject of several in vitro studies. However, simple stimuli were often applied, not fully mimicking the complex in vivo conditions. Therefore, a rolling/plowing explant test system (RPETS) was developed to replicate the combined in vivo loading patterns. In this work we investigated the mechanical behavior of bovine nasal septum (BNS) cartilage, selected as tissue approximation for experiments with RPETS, under static and dynamic loading. Biphasic material properties were determined and compared with those of other cartilaginous tissues. Furthermore, dynamic loading in plowing modality was performed to determine dynamic response and experimental results were compared with analytical models and Finite Elements (FE) computations. Results showed that BNS cartilage can be modeled as a biphasic material with Young's modulus E=2.03±0.7 MPa, aggregate modulus HA=2.35±0.7 MPa, Poisson's ratio ν=0.24±0.07, and constant hydraulic permeability k0=3.0±1.3×10−15 m4 (N s)−1. Furthermore, dynamic analysis showed that plowing induces macroscopic reactions in the tissue, proportionally to the applied loading force. The comparison among analytical, FE analysis and experimental results showed that predicted tangential forces and sample deformation lay in the range of variation of experimental results for one specific experimental condition. In conclusion, mechanical properties of BNS cartilage under both static and dynamic compression were assessed, showing that this tissue behave as a biphasic material and has a viscoelastic response to dynamic forces. 相似文献