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81.
Early environmental conditions may affect the development and manifestation of circadian rhythms. This study sought to determine whether the maintenance of rats under different T-cycles during lactation influences the subsequent degree of dissociation of the circadian rhythms of motor activity and core body temperature. Two groups of 22 day-old Wistar rats were kept after weaning under T-cycles of 22 h (T22) or 23 h (T23) for 70 days. Subsequently, they were kept in constant darkness (DD). Half of the animals in each group were born and reared under these experimental conditions, while the other half were reared until weaning under 24 h LD cycles (T24). Rats transferred from T24 to T22 or T23 showed two circadian components in motor activity and temperature, one entrained by light and the other free-running. In T22, there was also desynchronization between temperature and motor activity. Rats submitted to T23 from birth showed higher stability of the 23 h component than rats transferred from T24 to T23 after weaning. However, in comparison to rats born under T24 and subsequently changed to T22, animals submitted to T22 from birth showed shorter values of the period of the non-light-dependent component during T22, more aftereffects when transferred to DD, and a lack of desynchronization between motor activity and temperature. The results suggest that T-cycles in the early environment may modify overt rhythms by altering the internal coupling of the circadian pacemaker. 相似文献
82.
Catania MV D'Antoni S Bonaccorso CM Aronica E Bear MF Nicoletti F 《Molecular neurobiology》2007,35(3):298-307
Group I metabotropic glutamate receptors (mGlu1 and mGlu5) are coupled to polyphosphoinositide hydrolysis and are involved
in activity-dependent forms of synaptic plasticity, both during development and in the adult life. Group I mGlu receptors
can also regulate proliferation, differentiation, and survival of neural stem/progenitor cells, which further support their
role in brain development. An exaggerated response to activation of mGlu5 receptors may underlie synaptic dysfunction in Fragile
X syndrome, the most common inherited form of mental retardation. In addition, group I mGlu receptors are overexpressed in
dysplastic neurons of focal cortical dysplasia and hemimegaloencephaly, which are disorders of cortical development associated
with chronic epilepsy. Drugs that block the activity of group I mGlu receptors (in particular, mGlu5 receptors) are potentially
helpful for the treatment of Fragile X syndrome and perhaps other neurodevelopmental disorders. 相似文献
83.
Australia, the flattest, driest, and geologically oldest vegetated continent, has a uniquely high proportion of nutrient-poor soils. We develop a "Nutrient-Poverty/Intense-Fire Theory," which postulates that most anomalous features of organisms and ecosystems of Australia are the evolutionary consequences of adaptations to nutrient poverty, compounded by intense fire that tends to occur as a result of nutrient poverty. The fundamental tenet of the theory is that plants growing in environments with plentiful light and periodic adequate moisture, but on soils poor in phosphorus, zinc, and other indispensible nutrients, can synthesize carbohydrates in excess of the amount that can be combined with, or catalyzed by, these nutrients for metabolism and production of nutrient-rich foliage and reproductive tissues. They use this "expendable energy" to produce well-defended foliage, large quantities of lignified tissues, and readily digestible exudates. Rapid accumulation of nutrient-poor biomass, a result of low rates of herbivory, provides fuel for intense fire. Intense fire exacerbates nutrient poverty by volatilizing certain micronutrients critical for animals. Anomalous features of organisms of Australia that can be explained by this theory, rather than by climate or phylogenetic history alone, include the following: most woody plants have long-lived, durable foliage; plants defend their tissues primarily with carbon-rich but nutrient-poor compounds; an unusually high proportion of plants protects seeds from fire and granivores in sturdy, woody capsules or follicles; plants allocate unusually large amounts of expendable energy to production of carbon-based exudates, such as nectar and gums; an unusually high proportion of plant species is pollinated by vertebrates that average larger size than pollinators on other continents; herbivores are small and have slow metabolism; there are no ruminants, mammals that eat mainly subterranean plant matter, or fungus-culturing termites and ants; vegetation dominated by leaf-spinescent plants is more extensive than vegetation dominated by stem-spinescent plants; nitrogen-fixing plants are major components of most vegetation types; there is a higher proportion of myrmecochorous plant species than on any other continent; there are hardly any stem-succulent and few leaf-succulent, perennial, non-halophytic plant species; and an unusually high proportion of bird species breeds cooperatively. Although the Nutrient-Poverty/Intense-Fire Theory can provide plausible explanations for these anomalous features, some puzzles remain, among them the great success of introduced herbivores, the lack of grazers on extensive grasslands on cracking clays, the apparently low productivity of ants, and the prominence of the parasitic plants of Australia. By examining the ratios of available energy to nutrients, particularly scarce nutrients, ecologists may identify processes not previously recognized as important for life forms or biotic adaptation on other continents. 相似文献
84.
Noori Tayebeh Shirooie Samira Sureda Antoni Sobarzo-Sanchez Eduardo Dehpour Ahmad Reza Saldías Marianela Akkol Esra Küpeli 《Neurochemical research》2022,47(8):2142-2157
Neurochemical Research - Stroke is a sudden neurological disorder that occurs due to impaired blood flow to an area of the brain. Stroke can be caused by the blockage or rupture of a blood vessel... 相似文献
85.
Dalil Hannani Marie Vétizou David Enot Sylvie Rusakiewicz Nathalie Chaput David Klatzmann Melanie Desbois Nicolas Jacquelot Nadège Vimond Salem Chouaib Christine Mateus James P Allison Antoni Ribas Jedd D Wolchok Jianda Yuan Philip Wong Michael Postow Andrzej Mackiewicz Jacek Mackiewicz Dirk Schadendorff Dirk Jaeger Alan J Korman Keith Bahjat Michele Maio Luana Calabro Michele WL Teng Mark J Smyth Alexander Eggermont Caroline Robert Guido Kroemer Laurence Zitvogel 《Cell research》2015,25(2):208-224
The cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibody ipilimumab induces immune-mediated long-term control of metastatic melanoma in a fraction of patients. Although ipilimumab undoubtedly exerts its therapeutic effects via immunostimulation, thus far clinically useful, immunologically relevant biomarkers that predict treatment efficiency have been elusive. Here, we show that neutralization of IL-2 or blocking the α and β subunits of the IL-2 receptor (CD25 and CD122, respectively) abolished the antitumor effects and the accompanying improvement of the ratio of intratumoral T effector versus regulatory cells (Tregs), which were otherwise induced by CTLA-4 blockade in preclinical mouse models. CTLA-4 blockade led to the reduction of a suppressive CD4+ T cell subset expressing Lag3, ICOS, IL-10 and Egr2 with a concomitant rise in IL-2-producing effector cells that lost FoxP3 expression and accumulated in regressing tumors. While recombinant IL-2 improved the therapeutic efficacy of CTLA-4 blockade, the decoy IL-2 receptor α (IL-2Rα, sCD25) inhibited the anticancer effects of CTLA-4 blockade. In 262 metastatic melanoma patients receiving ipilimumab, baseline serum concentrations of sCD25 represented an independent indicator of overall survival, with high levels predicting resistance to therapy. Altogether, these results unravel a role for IL-2 and IL-2 receptors in the anticancer activity of CTLA-4 blockade. Importantly, our study provides the first immunologically relevant biomarker, namely elevated serum sCD25, that predicts resistance to CTLA-4 blockade in patients with melanoma. 相似文献
86.
Barberán A Fernández-Guerra A Auguet JC Galand PE Casamayor EO 《Molecular ecology》2011,20(9):1988-1996
Despite its widespread distribution and high levels of phylogenetic diversity, microbes are poorly understood creatures. We applied a phylogenetic ecology approach in the Kingdom Euryarchaeota (Archaea) to gain insight into the environmental distribution and evolutionary history of one of the most ubiquitous and largely unknown microbial groups. We compiled 16S rRNA gene sequences from our own sequence libraries and public genetic databases for two of the most widespread mesophilic Euryarchaeota clades, Lake Dagow Sediment (LDS) and Rice Cluster-V (RC-V). The inferred population history indicated that both groups have undergone specific nonrandom evolution within environments, with several noteworthy habitat transition events. Remarkably, the LDS and RC-V groups had enormous levels of genetic diversity when compared with other microbial groups, and proliferation of sequences within each single clade was accompanied by significant ecological differentiation. Additionally, the freshwater Euryarchaeota counterparts unexpectedly showed high phylogenetic diversity, possibly promoted by their environmental adaptability and the heterogeneous nature of freshwater ecosystems. The temporal phylogenetic diversification pattern of these freshwater Euryarchaeota was concentrated both in early times and recently, similarly to other much less diverse but deeply sampled archaeal groups, further stressing that their genetic diversity is a function of environment plasticity. For the vast majority of living beings on Earth (i.e. the uncultured microorganisms), how they differ in the genetic or physiological traits used to exploit the environmental resources is largely unknown. Inferring population history from 16S rRNA gene-based molecular phylogenies under an ecological perspective may shed light on the intriguing relationships between lineage, environment, evolution and diversity in the microbial world. 相似文献
87.
Screpanti E De Antoni A Alushin GM Petrovic A Melis T Nogales E Musacchio A 《Current biology : CB》2011,21(5):391-398
Kinetochores are proteinaceous scaffolds implicated in the formation of load-bearing attachments of chromosomes to microtubules during mitosis. Kinetochores contain distinct chromatin- and microtubule-binding interfaces, generally defined as the inner and outer kinetochore, respectively (reviewed in). The constitutive centromere-associated network (CCAN) and the Knl1-Mis12-Ndc80 complexes (KMN) network are the main multisubunit protein assemblies in the inner and outer kinetochore, respectively. The point of contact between the CCAN and the KMN network is unknown. Cenp-C is a conserved CCAN component whose central and C-terminal regions have been implicated in chromatin binding and dimerization. Here, we show that a conserved motif in the N-terminal region of Cenp-C binds directly and with high affinity to the Mis12 complex. Expression in HeLa cells of the isolated N-terminal motif of Cenp-C prevents outer kinetochore assembly, causing chromosome missegregation. The KMN network is also responsible for kinetochore recruitment of the components of the spindle assembly checkpoint, and we observe checkpoint impairment in cells expressing the Cenp-C N-terminal segment. Our studies unveil a crucial and likely universal link between the inner and outer kinetochore. 相似文献
88.
Alda M Luciano JV Andrés E Serrano-Blanco A Rodero B del Hoyo YL Roca M Moreno S Magallón R García-Campayo J 《Arthritis research & therapy》2011,13(5):R173
Introduction
No randomised, controlled trials have been conducted to date on the efficacy of psychological and pharmacological treatments of pain catastrophising (PC) in patients with fibromyalgia. Our aim in this study was to assess the effectiveness of cognitive-behaviour therapy (CBT) and the recommended pharmacological treatment (RPT) compared with treatment as usual (TAU) at the primary care level for the treatment of PC in fibromyalgia patients. 相似文献89.
Proteomic analysis of extracellular ATP-regulated proteins identifies ATP synthase beta-subunit as a novel plant cell death regulator 总被引:1,自引:0,他引:1
Chivasa S Tomé DF Hamilton JM Slabas AR 《Molecular & cellular proteomics : MCP》2011,10(3):M110.003905
Extracellular ATP is an important signal molecule required to cue plant growth and developmental programs, interactions with other organisms, and responses to environmental stimuli. The molecular targets mediating the physiological effects of extracellular ATP in plants have not yet been identified. We developed a well characterized experimental system that depletes Arabidopsis cell suspension culture extracellular ATP via treatment with the cell death-inducing mycotoxin fumonisin B1. This provided a platform for protein profile comparison between extracellular ATP-depleted cells and fumonisin B1-treated cells replenished with exogenous ATP, thus enabling the identification of proteins regulated by extracellular ATP signaling. Using two-dimensional difference in-gel electrophoresis and matrix-assisted laser desorption-time of flight MS analysis of microsomal membrane and total soluble protein fractions, we identified 26 distinct proteins whose gene expression is controlled by the level of extracellular ATP. An additional 48 proteins that responded to fumonisin B1 were unaffected by extracellular ATP levels, confirming that this mycotoxin has physiological effects on Arabidopsis that are independent of its ability to trigger extracellular ATP depletion. Molecular chaperones, cellular redox control enzymes, glycolytic enzymes, and components of the cellular protein degradation machinery were among the extracellular ATP-responsive proteins. A major category of proteins highly regulated by extracellular ATP were components of ATP metabolism enzymes. We selected one of these, the mitochondrial ATP synthase β-subunit, for further analysis using reverse genetics. Plants in which the gene for this protein was knocked out by insertion of a transfer-DNA sequence became resistant to fumonisin B1-induced cell death. Therefore, in addition to its function in mitochondrial oxidative phosphorylation, our study defines a new role for ATP synthase β-subunit as a pro-cell death protein. More significantly, this protein is a novel target for extracellular ATP in its function as a key negative regulator of plant cell death. 相似文献
90.
Tomàs Pinós Mario Marotta Eduard Gallardo Isabel Illa Jorge Díaz-Manera Emiliano Gonzalez-Vioque Elena García-Arumí Antoni L. Andreu Ramon Martí 《Mitochondrion》2011,11(1):228-233
We report a heteroplasmic novel mutation m.5636T>C in the mt-tRNAAla in a patient with bilateral ptosis and ophthalmoparesis in whom a muscle biopsy showed cytochrome c oxdidase (COX) negative and ragged red fibers. Using laser capture microdissection we have isolated COX negative fibers and COX positive fibers from the muscle of the patient and determined that the mutation load was clearly increased in COX negative muscle fibers. Additionally, the mutated m.5636T nucleotide is conserved in all the mammal and non-mammal species analyzed and might be structurally relevant as it is located in a position involved in the formation of tertiary structure of canonical mitochondrial tRNAs. 相似文献