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951.
Life span and aging are substantially modified by natural selection. Across species, higher extrinsic (environmentally related) mortality (and hence shorter life expectancy) selects for the evolution of more rapid aging. However, among populations within species, high extrinsic mortality can lead to extended life span and slower aging as a consequence of condition‐dependent survival. Using within‐species contrasts of eight natural populations of Nothobranchius fishes in common garden experiments, we demonstrate that populations originating from dry regions (with short life expectancy) had shorter intrinsic life spans and a greater increase in mortality with age, more pronounced cellular and physiological deterioration (oxidative damage, tumor load), and a faster decline in fertility than populations from wetter regions. This parallel intraspecific divergence in life span and aging was not associated with divergence in early life history (rapid growth, maturation) or pace‐of‐life syndrome (high metabolic rates, active behavior). Variability across four study species suggests that a combination of different aging and life‐history traits conformed with or contradicted the predictions for each species. These findings demonstrate that variation in life span and functional decline among natural populations are linked, genetically underpinned, and can evolve relatively rapidly.  相似文献   
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955.
Habitat loss and fragmentation are the leading causes of biodiversity decline world-wide. Animals sensitive to fragmentation experience reduced dispersal, breeding opportunities, and genetic diversity, making them vulnerable to local extinction. Over the last few decades the Atlantic Forest of Brazil has been extremely fragmented, with only 11–16% of forest remaining. The Brazilian government and nongovernmental organizations have taken actions through legislation and conservation initiatives to restore forest. Using computer modeling, we compared how alternative forest restoration strategies could improve functional connectivity for golden-headed lion tamarins (Leontopithecus chrysomelas) in Southern Bahia, Brazil. Strategies differed by restoration configuration, including Within- and Across-Property approaches, and restoration amount (0–20% restoration). Increasing restoration amounts resulted in greater species functional connectivity, and Within-Property and Across-Property strategies both had significantly more connectivity than the Random strategy. We suggest restoration management consider the size and placement of restored forest, and that riparian forest be restored first to create dispersal corridors and reestablish essential ecosystem services. We further suggest the importance of forming canopy bridges across narrow sections of rivers during the early stages of the restoration process to promote increased connectivity of these newly restored areas. Our findings can aid managers and landowners in understanding the implications of different restoration strategies for highly arboreal, matrix-sensitive species.  相似文献   
956.
The objective of this study was to explore the potential role of G-protein-coupled receptor kinase 2 (GRK2) in the progression of cannabinoid 2 receptor (CB2) agonist-induced analgesic effects of bone cancer pain. Female Sprague–Dawley rats, weighing 160–180 g, were utilized to establish a model of bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. JWH-015, a selective CB2 agonist, was injected intrathecally or intraperitoneally on postoperative day 10. Bone cancer-induced pain behaviors—mechanical allodynia and ambulatory pain—were assessed on postoperative days ?1 (baseline), 4, 7, and 10 and at post-treatment hours 2, 6, 24, 48, and 72. The expressions of spinal CB2 and GRK2 protein were detected by Western Blotting on postoperative days ?1 (baseline), 4, 7, and 10 and at post-treatment hours 6, 24, and 72. The procedure produced prolonged mechanical allodynia, ambulatory pain, and different changes in spinal CB2 and GRK2 expression levels. Intrathecal or intraperitoneal administration of JWH-015 alleviated the induced mechanical allodynia and ambulatory pain, and inhibited the downregulation of spinal GRK2 expression. These effects were in a time-dependent manner and reversed by pretreatment of CB2 selective antagonist AM630. The results affirmed CB2 receptor agonists might serve as new treatment targets for bone cancer pain. Moreover, spinal GRK2 was an important regulator of CB2 receptor agonist-analgesia pathway.  相似文献   
957.

Background

During the generation and evolution of the eukaryotic cell, a proteobacterial endosymbiont was re-fashioned into the mitochondrion, an organelle that appears to have been present in the ancestor of all present-day eukaryotes. Mitochondria harbor proteomes derived from coding information located both inside and outside the organelle, and the rate-limiting step toward the formation of eukaryotic cells may have been development of an import apparatus allowing protein entry to mitochondria. Currently, a widely conserved translocon allows proteins to pass from the cytosol into mitochondria, but how proteins encoded outside of mitochondria were first directed to these organelles at the dawn of eukaryogenesis is not clear. Because several proteins targeted by a carboxyl-terminal tail anchor (TA) appear to have the ability to insert spontaneously into the mitochondrial outer membrane (OM), it is possible that self-inserting, tail-anchored polypeptides obtained from bacteria might have formed the first gate allowing proteins to access mitochondria from the cytosol.

Results

Here, we tested whether bacterial TAs are capable of targeting to mitochondria. In a survey of proteins encoded by the proteobacterium Escherichia coli, predicted TA sequences were directed to specific subcellular locations within the yeast Saccharomyces cerevisiae. Importantly, TAs obtained from DUF883 family members ElaB and YqjD were abundantly localized to and inserted at the mitochondrial OM.

Conclusions

Our results support the notion that eukaryotic cells are able to utilize membrane-targeting signals present in bacterial proteins obtained by lateral gene transfer, and our findings make plausible a model in which mitochondrial protein translocation was first driven by tail-anchored proteins.

Reviewers

This article was reviewed by Michael Ryan and Thomas Simmen.
  相似文献   
958.
The geometry configuration of charged armchair graphene nanoribbons (AGNRs) is theoretically investigated in the framework of a two-dimensional tight-binding model that includes lattice relaxation. Our findings show that the charge distribution and, consequently, the bond length pattern is dependent on the parity of the nanoribbon width. In this sense, the lattice distortions decrease smoothly for increasingly wider GNRs. As should be expected, AGNRs belonging to a particular family present similar patterns for the bond lengths. The interplay between the electron-phonon coupling and band gap is also investigated. The results show that the electron-phonon coupling strength is fundamental to promote the transition from metallic towards semiconducting-like behavior for the band gap. Most important, such strength is crucial on defining the degree of lattice distortions in AGNRs.  相似文献   
959.
The activation mechanism of dopamine receptors is unknown. The amino acids S5.42, S5.43, and S5.46 located in helix 5 appear to be crucial, but their specific roles in receptor activation have not been studied. We modeled the D1 dopamine receptor using the crystal structures of the D3 dopamine and β2 adrenergic receptors. Molecular dynamics simulations show that the interaction of dopamine with the D1 receptor leads to the formation of a hydrogen-bond network with its catechol group and helices 3, 5, and 6, including water molecules. The para hydroxyl group of dopamine binds directly to S5.42 and N6.55, the latter also interacting with S5.43. Unexpectedly, S5.46 does not interact directly with the catechol; instead, it interacts through a water molecule with S5.42 and directly with T3.37. The formation of this hydrogen-bond network, part of which was previously observed in docking studies with dopamine agonists, triggers the opening of the E6.30–R3.60 ionic lock associated with the activation of GPCRs. These changes do not occur in the unbonded (apo) receptor or when it is in a complex with the antagonist 3-methoxy-5,6,7,8,9,14-hexahydrodibenz[d,g]azecine. Our results provide valuable insight into the T3.37–S5.46–water–S5.43–ligand interaction, which may be crucial to the activation of the D1 dopamine receptor and should be considered during the design of novel agonists.
Graphical Abstract General representation of the relationship between the formation of the HBN and the opening of the R3.50–E6.30 ionic lock
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960.
Hormonal asynchronies during oestrus, related to the presence of suprabasal plasma-progesterone (P4) concentrations and a delayed ovulation, interfere with the fertility of repeat-breeder heifers (RBH). Since tubal dysfunction can occur in connection with hormonal asynchronies and constrained availability of fertile spermatozoa at the time of ovulation, the present study tested the hypothesis that frequent sperm deposition from onset of oestrus to ovulation may improve pregnancy rates in RBH. Five RBH and five virgin heifers (VH; controls) were repeatedly artificially inseminated (AI) at 6 h intervals from onset of oestrus to spontaneous ovulation. Hormone analyses revealed suprabasal P4 concentrations and a delay in the occurrence of the luteinising hormone (LH) surge, but a normal cortisol profile in RBH. Compared with controls, RBH presented longer interval from onset of oestrus to ovulation, and therefore, received more AIs. Pregnancy rates in RBH reached control levels (60%; NS), indicating that the hypothesis might be correct. Pregnancy rates in VH were below the expected range, presumably attributed to a deleterious influence of the frequent handling. The study suggests that pregnancy rates can be improved in RBH by frequent AI in relation to spontaneous ovulation. However, this practice of repeated manipulations, while seeming not to show adverse effects, lacks practicality for routine use.  相似文献   
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