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921.
Chao Wei Wei Zhang Qiong Zhou Chao Zhao Ying Du Qi Yan Zhuyi Li Jianting Miao 《Neurochemical research》2016,41(8):1924-1938
Increasing evidence has shown that specificity protein 1 (Sp1) is abnormally increased in the brains of subjects with Alzheimer’s disease (AD) and transgenic AD models. However, whether the Sp1 activation plays a critical role in the AD pathogenesis and selective inhibition of Sp1 activation may have a disease-modifying effect on the AD-like phenotypes remain elusive. In this study, we reported that Sp1 mRNA and protein expression were markedly increased in the brain of APPswe/PS1dE9 transgenic mice, whereas chronic administration of mithramycin A (MTM), a selective Sp1 inhibitor, potently inhibited Sp1 activation in the APPswe/PS1dE9 mice down to the levels of wild-type mice. Specifically, we found that MTM treatment resulted in a significant improvement of learning and memory deficits, a dramatic reduction in cerebral Aβ levels and plaque burden, a profound reduction in tau hyperphosphorylation, and a marked increase in synaptic marker in the APPswe/PS1dE9 mice. In addition, MTM treatment was powerfully effective in inhibiting amyloid precursor protein (APP) processing via suppressing APP, beta-site APP cleaving enzyme 1 (BACE1), and presenilin-1 (PS1) mRNA and protein expression to preclude Aβ production in the APPswe/PS1dE9 mice. Furthermore, MTM treatment strongly inhibited phosphorylated CDK5 and GSK3β signal pathways to reduce tau hyperphosphorylation in the APPswe/PS1dE9 mice. Collectively, our findings provide evidence that Sp1 activation may contribute to the AD pathogenesis and may serve as a novel therapeutic target in the treatment of AD. The present study highlights that selective Sp1 inhibitors may be considered as disease-modifying therapeutic agents for AD. 相似文献
922.
Johannes W. S. A. Osterloh Arjan C. Videler Gina M. P. Rossi Sebastiaan P. J. van Alphen 《Tijdschrift voor gerontologie en geriatrie》2018,49(5):210-212
Behavioural counselling by nurses can enhance quality of life in elderly with a personality disorder. Although nurses have a crucial role in day-to-day treatment, there is a lack of evidence-based approaches. Based on the cognitive therapy, the treatment protocol Cognitive Model for Behavioural Interventions (CoMBI) provides an alternative nursing approach for personality disorders. 相似文献
923.
924.
Dalia Rokhsana David M. Dooley Robert K. Szilagyi 《Journal of biological inorganic chemistry》2008,13(3):371-383
A systematic in silico approach has been employed to generate sound, experimentally validated active-site models for galactose oxidase (GO) using a hybrid density functional, B(38HF)P86. GO displays three distinct oxidation states: oxidized [Cu(II)-Y*]; semireduced [Cu(II)-Y]; and reduced [Cu(I)-Y]. Only the [Cu(II)-Y*] and the [Cu(I)-Y] states are assumed to be involved in the catalytic cycle, but their structures have not yet been determined. We have developed several models (1-7) for the [Cu(II)-Y*] state that were evaluated by comparison of our computational results with experimental data. An extended model system (6) that includes solvent molecules and second coordination sphere residues (R330, Y405, and W290) is essential to obtain an experimentally correct electronic structure of the active site. The optimized structure of 6 resulted in a five-coordinate Cu site with a protein radical centered on the Tyr-Cys cofactor. We further validated our converged model with the largest model (7) that included additional outer-sphere residues (Q406, H334, Y329, G513, and T580) and water molecules. Adding these residues did not affect significantly the active site's electronic and geometric structures. Using both 6 and 7, we explored the redox dependence of the active-site structure. We obtained four- and three-coordinate Cu sites for [Cu(II)-Y] and [Cu(I)-Y] states, respectively, that corroborate well with the experimental data. The relative energies of these states were validated by a comparison with experimental redox potentials. Collectively, our computational GO models well reproduce the physicochemical characteristics of the individual states, including their redox behaviors. 相似文献
925.
Vanesa M. Fernández Andrés Arenas Walter M. Farina 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2009,195(8):759-768
Honeybees of different ages and reproductive castes cohabit in the hive where they are exposed to many odors that might affect
associative learning. Our aim was to analyze the role of odors pre-exposed as volatiles on appetitive learning in honeybees
of different ages and search for their long-term effect both under natural and laboratory conditions. By evaluating memory
acquisition and retention through a differential proboscis extension response conditioning, we found that hive-exposed odors
offered as a reinforced conditioned stimulus during training promoted a learning-reduced effect [latent inhibition (LI)].
On the other hand, no effect was found when the non-reinforced conditioned stimulus was pre-exposed. The LI effect varied
with the odor identity. However, only slight differences were found with the age of the bees. Exposure-conditioning intervals
longer than 24 h did not show an LI effect unless the odor concentration was increased or exposure was prolonged. Our results
show that pre-exposed volatiles could either reduce learning performance, if this odor is later associated with food, or be
irrelevant in the case that alternative scented resources circulate within the colony. The differential effects found according
to the olfactory exposure characteristics could strongly influence the propagation of chemosensory information within the
hive. 相似文献
926.
Hernandez-Pigeon H Jean C Charruyer A Haure MJ Titeux M Tonasso L Quillet-Mary A Baudouin C Charveron M Laurent G 《The Journal of biological chemistry》2006,281(19):13525-13532
Ultraviolet (UV) radiation from the sun is widely considered as a major cause of human skin photoaging and skin cancer. Granzyme B (GrB) and perforin (PFN) are two proteins contained in granules and implicated in one of the mechanisms by which cytotoxic lymphocytes and natural killer cells exert their cytotoxicity against virus-infected, alloreactive, or transformed cells. The distribution of GrB and PFN in the skin has received little attention. However, Berthou and co-workers (Berthou, C., Michel, L., Soulie, A., Jean-Louis, F., Flageul, B., Dubertret, L., Sigaux, F., Zhang, Y., and Sasportes, M. (1997) J. Immunol. 159, 5293-5300) described that, whereas freshly isolated epidermal cells did not express GrB or PFN, keratinocyte growth to confluence was associated with GrB and PFN mRNA and protein synthesis. In this work, we have investigated the possible role of UV-B on GrB and PFN expression in keratinocytes. We found that UV-B induces GrB and PFN expression in these cells through redox-, epidermal growth factor receptor-, and mitogen-activated protein kinase-dependent signaling. Furthermore, under UV irradiation, keratinocytes acquire a significant cytotoxicity, which is GrB and PFN dependent, toward a variety of cellular targets including transformed T-lymphocytes, melanocytes, and keratinocytes. This phenomenon may have important functional consequences in the regulation of skin inflammatory response and in the emergence of cancer skin. 相似文献
927.
Judith Zhi-Yie Tan Stephen M Schlicht Gerard J Powell David Thomas John L Slavin Peter J Smith Peter FM Choong 《International Seminars in Surgical Oncology : ISSO》2006,3(1):38
Background
Osteosarcoma is the most common primary malignant bone tumour in children and young adults. Despite advances in the diagnosis and management of osteosarcoma, there have been few recent studies describing the experiences of tertiary referral centres. This paper aims to describe and discuss the clinical features, pre-operative work-up, management and outcomes of these patients at St Vincent's Hospital (Melbourne, Australia).Methods
Retrospective study of fifty-nine consecutive patients managed for osteosarcoma at St Vincent's Hospital between 1995 and 2005.Results
Median age at diagnosis was 21 (range, 11–84) years. Gender distribution was similar, with thirty-one male and twenty-eight female patients.Twenty-five patients had osteosarcoma in the femur, eleven each were located in the humerus and tibia, six were identified in the pelvis, and one each in the clavicle, maxilla, fibula, sacrum, ulna and radius.Pre-operative tissue diagnosis of osteosarcoma was obtained through computed tomography-guided percutaneous biopsy in over ninety percent of patients.Following initial therapy, over fifty percent of patients remained relapse-free during the follow-up period, with twelve percent and twenty-seven percent of patients documented as having local and distant disease recurrence, respectively. Of patients with recurrent disease, sixty-two percent remained disease-free following subsequent surgical intervention (most commonly, pulmonary metastatectomy).Conclusion
Patient outcomes can be optimised through a multidisciplinary approach in a tertiary referral centre. At St Vincent's Hospital, survival and relapse rates of patients managed for osteosarcoma compare favourably with the published literature.928.
The promoter of the pepper pathogen-induced membrane protein gene CaPIMP1 was analyzed by an Agrobacterium-mediated transient expression assay in tobacco leaves. Several stress-related cis-acting elements (GT-1, W-box and ABRE) are located within the CaPIMP1 promoter. In tobacco leaf tissues transiently transformed with a CaPIMP1 promoter-β-glucuronidase (GUS) gene fusion, serially 5′-deleted CaPIMP1 promoters were differentially activated by Pseudomonas syringae pv. tabaci, ethylene, methyl jasmonate, abscisic acid, and nitric oxide. The −1,193 bp region of the CaPIMP1 gene promoter sequence exhibited full promoter activity. The −417- and −593 bp promoter regions were sufficient for GUS gene activation by ethylene and methyl jasmonate treatments, respectively. However, CaPIMP1 promoter sequences longer than −793 bp were required for promoter activation by abscisic acid and sodium nitroprusside treatments.
CaPIMP1 expression was activated in pepper leaves by treatment with ethylene, methyl jasmonate, abscisic acid, β-amino-n-butyric acid, NaCl, mechanical wounding, and low temperature, but not with salicylic acid. Overexpression of CaPIMP1 in Arabidopsis conferred hypersensitivity to mannitol, NaCl, and ABA during seed germination but not during seedling development. In contrast,
transgenic plants overexpressing CaPIMP1 exhibited enhanced tolerance to oxidative stress induced by methyl viologen during germination and early seedling stages.
These results suggest that CaPIMP1 expression may alter responsiveness to environmental stress, as well as to pathogen infection.
The nucleotide sequence data reported here has been deposited in the GenBank database under the accession number DQ356279. 相似文献
929.
Nitric oxide (NO) is an important molecule that acts in many tissues to regulate a diverse range of physiological processes.
It is becoming apparent that NO is a ubiquitous signal in plants. Since the discovery of NO emission by plants in the 1970s,
this gaseous compound has emerged as a major signalling molecule involved in multiple physiological functions. Research on
NO in plants has gained significant awareness in recent years and there is increasing indication on the role of this molecule
as a key-signalling molecule in plants. The investigations about NO in plants have been concentrated on three main fields:
The search of NO or any source of NO generation, effects of exogenous NO treatments, NO transduction pathways. However we
have limited information about signal transduction procedures by which NO interaction with cells results in altered cellular
activities. This article reviews recent advances in NO synthesis and its signalling functions in plants. First, different
sources and biosynthesis of NO in plants, then biological processes involving NO signalling are reviewed. NO signalling relation
with cGMP, protein kinases and programmed cell death are also discussed. Besides, NO signalling in plant defense response
is also examined. Especially NO signalling between animal and plant systems is compared. 相似文献
930.
The occipital cortex (OC) of early-blind humans is activated during various nonvisual perceptual and cognitive tasks, but little is known about its modular organization. Using functional MRI we tested whether processing of auditory versus tactile and spatial versus nonspatial information was dissociated in the OC of the early blind. No modality-specific OC activation was observed. However, the right middle occipital gyrus (MOG) showed a preference for spatial over nonspatial processing of both auditory and tactile stimuli. Furthermore, MOG activity was correlated with accuracy of individual sound localization performance. In sighted controls, most of extrastriate OC, including the MOG, was deactivated during auditory and tactile conditions, but the right MOG was more activated during spatial than nonspatial visual tasks. Thus, although the sensory modalities driving the neurons in the reorganized OC of blind individuals are altered, the functional specialization of extrastriate cortex is retained regardless of visual experience. 相似文献