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121.
Marco Girardello Matteo Griggio Mark J. Whittingham Stephen P. Rushton 《Ecological Research》2010,25(1):103-111
Analyzing the relationships between the distribution of animal species and climatic variables is not only important for understanding
which factors govern species distribution but also for improving our ability to predict future ecological responses to climate
change. In the context of global climate change, amphibians are of particular interest because of their extreme sensitivity
to the variation of temperature and precipitation regimes. We analyzed species–climate relationships for 17 amphibian species
occurring in Italy using species distribution data at the 10 × 10 km resolution. A machine learning method, Random Forests,
was used to model the distribution of amphibians in relation to a set of 18 climatic variables. The results showed that the
variables which had the highest importance were those related to precipitation, indicating that precipitation is an important
factor in determining amphibian distribution. Future projections showed a complex response of species distributions, emphasizing
the potential severity of climate change on the distributions of amphibians in Italy. The species that will decrease the most
are those occurring in mountainous and Mediterranean areas. Our results provide some preliminary information that could be
useful for amphibian conservation, indicating if future conservation priorities for some species should be enhanced. 相似文献
122.
Rachele Beghin Emanuele Lingua Matteo Garbarino Michele Lonati Giovanni Bovio Renzo Motta Raffaella Marzano 《Ecological Engineering》2010,36(10):1365-1372
It is frequently believed that a post-fire environment requires immediate actions in order to be restored. Salvage logging followed by plantation is a common post-fire restoration practice in many forests of the northwestern Italian Alps.The objectives of this study were to assess the impact of active and passive management techniques on the restoration of a burned area of the Aosta Valley and to determine which approach is the most suitable for enhancing Pinus sylvestris regeneration after stand replacing wildfires.The influence of five management options (no intervention; salvage logging; broadleaves plantation; Larix decidua plantation; P. sylvestris or Pseudotsuga menziesii plantation) and environmental variables on natural regeneration structure and composition was evaluated through direct gradient analysis.Pinus sylvestris and Populus tremula were the dominant tree species (40 and 29%, respectively) in the regeneration layer. Density, size, and structural diversity of natural regeneration were higher in the no intervention area. The proximity to forest edge was found to be the most important environmental variable.This study provided evidence that taking advantage of natural restoration processes may be a suitable alternative strategy to the active restoration practices adopted according to the Aosta Valley policy of post-fire management. 相似文献
123.
The identification of a series of novel, soluble non-peptidic neuropeptide Y Y2 receptor antagonists
Lunniss GE Barnes AA Barton N Biagetti M Bianchi F Blowers SM Caberlotto LL Emmons A Holmes IP Montanari D Norris R Puckey GV Walters DJ Watson SP Willis J 《Bioorganic & medicinal chemistry letters》2010,20(24):7341-7344
The identification and subsequent optimisation of a selective non-peptidic NPY Y2 antagonist series is described. This led to the development of amine 2, a selective, soluble NPY Y2 receptor antagonist with enhanced CNS exposure. 相似文献
124.
Debora Paris Dominique Melck Matteo Stocchero Oceania D’Apolito Rosa Calemma Giuseppe Castello Francesco Izzo Giuseppe Palmieri Gaetano Corso Andrea Motta 《Metabolomics : Official journal of the Metabolomic Society》2010,6(3):405-416
Human hepatocellular carcinoma (HCC) is the most recurrent malignancy of the liver and represents one of the main causes of
cancer death worldwide. Furthermore, the liver is the most frequent site of metastatic colonization, and hepatic metastases
are far more common than primary cancers in Western countries. A possible way of investigating liver diseases is to study
the tissue metabolic profiles. High-resolution nuclear magnetic resonance (NMR) spectroscopy of hepatic tissue extracts was
combined with pattern-recognition and visualization techniques to uncover metabolic differences among analyzed tissue types.
Extracts were from primary HCC, chronic hepatitis-C-virus related cirrhotic tissues, hepatic metastases from colorectal carcinomas,
and non-cirrhotic normal liver tissues adjacent to metastases as controls. We identified all metabolites present in the NMR
spectra, and after statistical evaluation of all spectral classes, we were able to define the metabolic changes underlying
the different liver conditions and diseases. In particular, the lactate and the glucose tissue signals were found to primarily
discriminate the different histological samples. We followed the biochemical changes of human hepatic lesions through primary
(HCC) and secondary (metastases from colorectal carcinoma) liver tumors, cirrhotic tissues, and non-cirrhotic histologically-confirmed
normal liver tissues adjacent to metastases, achieving a metabolic differentiation of the various pathological states based
upon the variation of the intracellular lactate/glucose ratio. It is suggested that such a signal pattern may act as a potential
marker for assessing pathological hepatic lesions. 相似文献
125.
Maila Giannandrea Maria Lidia Mignogna Salvatore Carrabino Matteo Vecellio Silvia Russo Lidia Larizza Hans-Hilger Ropers Vera Kalscheuer Cindy Skinner Jozef Gecz Hilde Van Esch Jamel Chelly Daniela Toniolo Patrizia D'Adamo 《American journal of human genetics》2010,86(2):185-195
Human Mental Retardation (MR) is a common and highly heterogeneous pediatric disorder affecting around 3% of the general population; at least 215 X-linked MR (XLMR) conditions have been described, and mutations have been identified in 83 different genes, encoding proteins with a variety of function, such as chromatin remodeling, synaptic function, and intracellular trafficking. The small GTPases of the RAB family, which play an essential role in intracellular vesicular trafficking, have been shown to be involved in MR. We report here the identification of mutations in the small GTPase RAB39B gene in two male patients. One mutation in family X (D-23) introduced a stop codon seven amino acids after the start codon (c.21C > A; p.Y7X). A second mutation, in the MRX72 family, altered the 5′ splice site (c.215+1G > A) and normal splicing. Neither instance produced a protein. Mutations segregate with the disease in the families, and in some family members intellectual disabilities were associated with autism spectrum disorder, epileptic seizures, and macrocephaly. We show that RAB39B, a novel RAB GTPase of unknown function, is a neuronal-specific protein that is localized to the Golgi compartment. Its downregulation leads to an alteration in the number and morphology of neurite growth cones and a significant reduction in presynaptic buttons, suggesting that RAB39B is required for synapse formation and maintenance. Our results demonstrate developmental and functional neuronal alteration as a consequence of downregulation of RAB39B and emphasize the critical role of vesicular trafficking in the development of neurons and human intellectual abilities. 相似文献
126.
Osmotic loading of spherical gels: a biomimetic study of hindered transport in the cell protoplasm 总被引:1,自引:0,他引:1
Albro MB Chahine NO Caligaris M Wei VI Likhitpanichkul M Ng KW Hung CT Ateshian GA 《Journal of biomechanical engineering》2007,129(4):503-510
Osmotic loading of cells has been used to investigate their physicochemical properties as well as their biosynthetic activities. The classical Kedem-Katchalsky framework for analyzing cell response to osmotic loading, which models the cell as a fluid-filled membrane, does not generally account for the possibility of partial volume recovery in response to loading with a permeating osmolyte, as observed in some experiments. The cell may be more accurately represented as a hydrated gel surrounded by a semi-permeable membrane, with the gel and membrane potentially exhibiting different properties. To help assess whether this more elaborate model of the cell is justified, this study investigates the response of spherical gels to osmotic loading, both from experiments and theory. The spherical gel is described using the framework of mixture theory. In the experimental component of the study alginate is used as the model gel, and is osmotically loaded with dextran solutions of various concentrations and molecular weight, to verify the predictions from the theoretical analysis. Results show that the mixture framework can accurately predict the transient and equilibrium response of alginate gels to osmotic loading with dextran solutions. It is found that the partition coefficient of dextran in alginate regulates the equilibrium volume response and can explain partial volume recovery based on passive transport mechanisms. The validation of this theoretical framework facilitates future investigations of the role of the protoplasm in the response of cells to osmotic loading. 相似文献
127.
Levisetti MG Suri A Petzold SJ Unanue ER 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(10):6051-6057
Several naturally occurring anti-insulin CD4 T cells were isolated from islet infiltrates of NOD mice. In accordance with the results of others, these T cells recognized the segment of the beta-chain from residues 9-23. Peptides encompassing the B:(9-23) sequence bound weakly to I-Ag7 in two main contiguous registers in which two residues at the carboxyl end, P20Gly and P21Glu, influenced binding and T cell reactivity. Naturally occurring insulin-reactive T cells exhibited differing reactivities with the carboxyl-terminal amino acids, although various single residue changes in either the flanks or the core segments affected T cell responses. The insulin peptides represent another example of a weak MHC-binding ligand that is highly immunogenic, giving rise to distinct populations of autoimmune T cells. 相似文献
128.
Tochowicz A Maskos K Huber R Oltenfreiter R Dive V Yiotakis A Zanda M Pourmotabbed T Bode W Goettig P 《Journal of molecular biology》2007,371(4):989-1006
Human matrix metalloproteinase 9 (MMP-9), also called gelatinase B, is particularly involved in inflammatory processes, bone remodelling and wound healing, but is also implicated in pathological processes such as rheumatoid arthritis, atherosclerosis, tumour growth, and metastasis. We have prepared the inactive E402Q mutant of the truncated catalytic domain of human MMP-9 and co-crystallized it with active site-directed synthetic inhibitors of different binding types. Here, we present the X-ray structures of five MMP-9 complexes with gelatinase-specific, tight binding inhibitors: a phosphinic acid (AM-409), a pyrimidine-2,4,6-trione (RO-206-0222), two carboxylate (An-1 and MJ-24), and a trifluoromethyl hydroxamic acid inhibitor (MS-560). These compounds bind by making a compromise between optimal coordination of the catalytic zinc, favourable hydrogen bond formation in the active-site cleft, and accommodation of their large hydrophobic P1' groups in the slightly flexible S1' cavity, which exhibits distinct rotational conformations of the Pro421 carbonyl group in each complex. In all these structures, the side-chain of Arg424 located at the bottom of the S1' cavity is not defined in the electron density beyond C(gamma), indicating its mobility. However, we suggest that the mobile Arg424 side-chain partially blocks the S1' cavity, which might explain the weaker binding of most inhibitors with a long P1' side-chain for MMP-9 compared with the closely related MMP-2 (gelatinase A), which exhibits a short threonine side-chain at the equivalent position. These novel structural details should facilitate the design of more selective MMP-9 inhibitors. 相似文献
129.
Metabotropic glutamate receptor type 5 (mGluR5) modulates dopamine and glutamate neurotransmission at central synapses. In this study, we addressed the role of mGluR5 in l-DOPA-induced dyskinesia, a movement disorder that is due to abnormal activation of both dopamine and glutamate receptors in the basal ganglia. A selective and potent mGluR5 antagonist, 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl] pyridine, was tested for its ability to modulate molecular, behavioural and neurochemical correlates of dyskinesia in 6-hydroxydopamine-lesioned rats treated with l-DOPA. The compound significantly attenuated the induction of abnormal involuntary movements (AIMs) by chronic l-DOPA treatment at doses that did not interfere with the rat physiological motor activities. These effects were paralleled by an attenuation of molecular changes that are strongly associated with the dyskinesiogenic action of l-DOPA (i.e. up-regulation of prodynorphin mRNA in striatal neurons). Using in vivo microdialysis, we found a temporal correlation between the expression of l-DOPA-induced AIMs and an increased GABA outflow within the substantia nigra pars reticulata. When co-administered with l-DOPA, 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl] pyridine greatly attenuated both the increase in nigral GABA levels and the expression of AIMs. These data demonstrate that mGluR5 antagonism produces strong anti-dyskinetic effects in an animal model of Parkinson's disease through central inhibition of the molecular and neurochemical underpinnings of l-DOPA-induced dyskinesia. 相似文献
130.
Cytosolic activation of cathepsins mediates parvovirus H-1-induced killing of cisplatin and TRAIL-resistant glioma cells 下载免费PDF全文
Di Piazza M Mader C Geletneky K Herrero Y Calle M Weber E Schlehofer J Deleu L Rommelaere J 《Journal of virology》2007,81(8):4186-4198
Gliomas are often resistant to the induction of apoptotic cell death as a result of the development of survival mechanisms during astrocyte malignant transformation. In particular, the overexpression of Bcl-2-family members interferes with apoptosis initiation by DNA-damaging agents (e.g., cisplatin) or soluble death ligands (e.g., TRAIL). Using low-passage-number cultures of glioma cells, we have shown that parvovirus H-1 is able to induce death in cells resistant to TRAIL, cisplatin, or both, even when Bcl-2 is overexpressed. Parvovirus H-1 triggers cell death through both the accumulation of lysosomal cathepsins B and L in the cytosol of infected cells and the reduction of the levels of cystatin B and C, two cathepsin inhibitors. The impairment of either of these effects protects glioma cells from the viral lytic effect. In normal human astrocytes, parvovirus H-1 fails to induce a killing mechanism. In vivo, parvovirus H-1 infection of rat glioma cells intracranially implanted into recipient animals triggers cathepsin B activation as well. This report identifies for the first time cellular effectors of the killing activity of parvovirus H-1 against malignant brain cells and opens up a therapeutic approach which circumvents their frequent resistance to other death inducers. 相似文献