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951.
Vianello A Casolo V Petrussa E Peresson C Patui S Bertolini A Passamonti S Braidot E Zancani M 《Biochimica et biophysica acta》2012,1817(11):2072-2086
The mitochondrial permeability transition (PT) is a well-recognized phenomenon that allows mitochondria to undergo a sudden increase of permeability to solutes with molecular mass ≤ 1500Da, leading to organelle swelling and structural modifications. The relevance of PT relies on its master role in the manifestation of programmed cell death (PCD). This function is performed by a mega-channel (in some cases inhibited by cyclosporin A) named permeability transition pore (PTP), whose function could derive from the assembly of different mitochondrial proteins. In this paper we examine the distribution and characteristics of PTP in mitochondria of eukaryotic organisms so far investigated in order to draw a hypothesis on the mechanism of its evolution. As a result, we suggest that PTP may have arisen as a new function linked to a multiple molecular exaptation of different mitochondrial proteins, even though they could nevertheless still play their original role. Furthermore, we suggest that the early appearance of PTP could have had a crucial role in the establishment of endosymbiosis in eukaryotic cells, by the coordinated balancing of ATP production by glycolysis (performed by the primary phagocyte) and oxidative phosphorylation (accomplished by the endosymbiont). Indeed, we argue on the possibility that this new energetic equilibrium could have opened the way to the subsequent evolution toward metazoans. 相似文献
952.
Codazzi D Bruschi S Bocchiotti MA Robotti E 《Plastic and reconstructive surgery》2012,129(6):999e-1000e; author reply 1000e-1001e
953.
Frascaroli E Canè MA Pè ME Pea G Landi P 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2012,124(1):35-47
In a previous study on a maize (Zea mays L.) population of recombinant inbreds derived from B73 × H99, we identified several quantitative trait loci (QTL) for agronomic
traits with high dominance-additive ratio. Then, for four of these QTL, we developed families of near-isogenic lines (NILs)
homozygous either for the QTL allele from B73 (BB) or from H99 (HH); for two of these QTL, the NILs’ families were produced
in two different genetic backgrounds. The present study was conducted to: (1) characterize these QTL for agronomic traits
and (2) verify whether their effects were influenced by the genetic background, inbreeding level and plant density (PD). The
six NILs’ families were tested across 3 years and in three experiments at different inbreeding levels as NILs per se and their
reciprocal crosses (Experiment 1), NILs crossed to related inbreds B73 and H99 (Experiment 2) and NILs crossed to four unrelated
inbreds (Experiment 3). Experiment 2 was conducted at two PDs (4.5 and 9.0 plants m−2). Results of Experiments 1 and 2 confirmed previous findings as to QTL effects, with dominance–additive ratio superior to
1 for several traits; as a tendency, dominance effects were more pronounced in Experiment 1. The QTL effects were also confirmed
in Experiment 3. The interactions involving QTL effects, families and PD were generally negligible, suggesting a certain stability
of the QTL. Results emphasize the importance of dominance effects for these QTL, suggesting that they might deserve further
studies, using the NILs’ families and their crosses as base materials. 相似文献
954.
955.
Uccelli A Milanese M Principato MC Morando S Bonifacino T Vergani L Giunti D Voci A Carminati E Giribaldi F Caponnetto C Bonanno G 《Molecular medicine (Cambridge, Mass.)》2012,18(1):794-804
Despite some advances in the understanding of amyotrophic lateral sclerosis (ALS) pathogenesis, significant achievements in treating this disease are still lacking. Mesenchymal stromal (stem) cells (MSCs) have been shown to be effective in several models of neurological disease. To determine the effects of the intravenous injection of MSCs in an ALS mouse model during the symptomatic stage of disease, MSCs (1 × 106) were intravenously injected in mice expressing human superoxide dismutase 1 (SOD1) carrying the G93A mutation (SOD1/G93A) presenting with experimental ALS. Survival, motor abilities, histology, oxidative stress markers and [3H]d-aspartate release in the spinal cord were investigated. MSC injection in SOD1/G93A mice improved survival and motor functions compared with saline-injected controls. Injected MSCs scantly home to the central nervous system and poorly engraft. We observed a reduced accumulation of ubiquitin agglomerates and of activated astrocytes and microglia in the spinal cord of MSC-treated SOD1/G93A mice, with no changes in the number of choline acetyltransferase– and glutamate transporter type 1–positive cells. MSC administration turned around the upregulation of metallothionein mRNA expression and of the activity of the antioxidant enzyme glutathione S-transferase, both associated with disease progression. Last, we observed that MSCs reverted both spontaneous and stimulus-evoked neuronal release of [3H]d-aspartate, a marker of endogenous glutamate, which is upregulated in SOD1/G93A mice. These findings suggest that intravenous administration of MSCs significantly improves the clinical outcome and pathological scores of mutant SOD1/G93A mice, thus providing the rationale for their exploitation for the treatment of ALS. 相似文献
956.
Guidi F Puglia M Gabbiani C Landini I Gamberi T Fregona D Cinellu MA Nobili S Mini E Bini L Modesti PA Modesti A Messori L 《Molecular bioSystems》2012,8(4):985-993
Cytotoxic gold compounds hold today great promise as new pharmacological agents for treatment of human ovarian carcinoma; yet, their mode of action is still largely unknown. To shed light on the underlying molecular mechanisms, we performed 2D-DIGE analysis to identify differential protein expression in a cisplatin-sensitive human ovarian cancer cell line (A2780/S) following treatment with two representative gold(iii) complexes that are known to be potent antiproliferative agents, namely AuL12 and Au(2)Phen. Software analysis using DeCyder was performed and few differentially expressed protein spots were visualized between the three examined settings after 24 h exposure to the cytotoxic compounds, implying that cellular damage at least during the early phases of exposure is quite limited and selective, reflecting the attempts of the cell to repair damage and to survive the insult. The potential of novel proteomic methods to disclose mechanistic details of cytotoxic metallodrugs is herein further highlighted. Different patterns of proteomic changes were highlighted for the two metallodrugs with only a few perturbed protein spots in common. Using MALDI-TOF MS and ESI-Ion trap MS/MS, several differentially expressed proteins were identified. Two of these were validated by western blotting: Ubiquilin-1, responsible for inhibiting degradation of proteins such as p53 and NAP1L1, a candidate marker identified in primary tumors. Ubiquilin-1 resulted over-expressed following both treatments and NAP1L1 was down-expressed in AuL12-treated cells in comparison with control and with Au(2)Phen-treated cells. In conclusion, we performed a comprehensive analysis of proteins regulated by AuL12 and Au(2)Phen, providing a useful insight into their mechanisms of action. 相似文献
957.
The visualization and quantification of mitochondria-associated proteins with high power microscopy methods is of particular interest to investigate protein architecture in this organelle. We report the usage of a custom-made STimulated Emission Depletion (STED) fluorescence nanoscope with ~30nm lateral resolution for protein mapping of Percoll-purified viable mitochondria from murine heart. Using this approach, we were able to quantify and resolve distinct protein clusters within mitochondria; specifically, cytochrome c oxidase subunit 2 is distributed in clusters of ~28nm; whereas the voltage dependent anion channel 1 displays three size distributions of ~33, ~55 and ~83nm. 相似文献
958.
In yeast, DNA polymerase zeta (Rev3 and Rev7) and Rev1, involved in the error-prone translesion synthesis during replication of nuclear DNA, localize also in mitochondria. We show that overexpression of Rev3 reduced the mtDNA extended mutability caused by a subclass of pathological mutations in Mip1, the yeast mitochondrial DNA polymerase orthologous to human Pol gamma. This beneficial effect was synergistic with the effect achieved by increasing the dNTPs pools. Since overexpression of Rev3 is detrimental for nuclear DNA mutability, we constructed a mutant Rev3 isoform unable to migrate into the nucleus: its overexpression reduced mtDNA mutability without increasing the nuclear one. 相似文献
959.
Giandomenico Passavanti Valerio Pizzuti Enrico Spinosa Alessandro Bragaglia Riccardo Paolini 《Andrologie》2005,15(4):374-377
Testicular microlithiasis (TMI) is a rare and little known condition. We verified its clinical and pathogenetic characteristics according to our experience. We performed testicular echography on four patients. Three of them had subfertlity and presented oligoasthenospermia in the spermiogram, while one patient had prostatitis with emospermia. Three patients had a high density TMI and one had a low density TMI. None of them showed neoplastic testicular lesions in the first echography. Anamnesis and examination revealed no outstanding data, one had been treated with calcium and Vit.D when a child for rachitis and another reported acute orchyepididymitis in his past history. Oncological markers were negative. 6–18 months follow-up with examination and echography didn’t show any testicular nodules. TMI is easy to diagnose and classify thanks to echography: Isolated TMI (the commonest, of flogistic, vascular or post-traumatic origin) Low-density TMI (<5calcifications per scan) High-density TMI (>5 calcifications per scan). Aetiology, pathogenesis of TMI and its connection to testicular cancer are not yet known. Differential diagnosis trhough echography is possible with both pathological hyperechogenic lesions of testicles (i.e. Tumors, hoematomas, partial atrophy, torsion, calcified hydatid) and non pathological ones (ilum, testicular mediastinum). The structure of the calcifications is constituted by hydroxyapatite which develop on degenerated spermatogones. They measure 1–3mm in diameter and can be found on 30–75% of the seminifer tubules. TMI is typical of patients with subfertility although the connection between this condition and male sterility is not clear. Similarly, TMI can be found in testicles’ tumours although even in this case, the connection between these conditions is not clear. That is why all authors agree in suggesting an echographical check every 6–12 months. Although the above case history can’t be considered significant due to the small number of patients, it is interesting to notice how 3 out of 4 patients had subfertility. Follow-up never showed probable neoplastic lesions. Finally what we also found worthy of notice is the possible connection between past orchyepididymitis and TML and connection between therapy for rachitis and TMI. 相似文献
960.
Karl-Heinz Herrmann Enrico Wagner Andreas Deistung Ingrid Hilger Jürgen R Reichenbach 《Biomedizinische Technik》2008,53(3):138-144
An increasing number of animal experiments are currently conducted on clinical MR systems. Motion artefacts due to breathing can become quite apparent, in particular with abdominal examinations. These artefacts can be reduced by using a triggered acquisition. However, the built-in detectors in human whole-body scanners are usually not sensitive enough to detect the tiny movements of small rodents. Therefore, a sensitive optical motion detector was developed together with a simple, robust analogue circuit. This circuit converts the original optical signal into an electrical one, compensates slow drifts and offsets, and finally generates a transistor-transistor logic trigger signal as input for the clinical whole-body magnetic resonance scanner. The trigger was successfully applied in mouse experiments. 相似文献