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61.
Diego Bellavia Alessandro Cataliotti Francesco Clemenza Cesar Hernandez Baravoglia Angelo Luca Marcello Traina Bruno Gridelli Tullio Bertani John C. Burnett Cesare Scardulla 《PloS one》2015,10(11)
Background and Aims
Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs in the remaining kidney. However, the long-term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs), approximately 12 years after UNX.Methods and Results
Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years) was investigated and compared to those of age and sex matched U.S. citizens healthy controls (n = 15). Standard and speckle tracking echocardiography (STE) was performed in both LKDs and controls. Plasma angiotensin II, aldosterone, atrial natriuretic peptide (ANP), N terminus pro B-type natriuretic peptide (NT-proBNP), cyclic guanylyl monophosphate (cGMP), and amino-terminal peptide of procollagen III (PIIINP) were also collected. Median follow-up was 11.9 years. In LKDs, LV geometry and function by STE were similar to controls, wall thickness and volumes were within normal limits also by CMR. In LKDs, CMR was negative for myocardial fibrosis, but apical rotation and LV torsion obtained by STE were impaired as compared to controls (21.4 ± 7.8 vs 32.7 ± 8.9 degrees, p = 0.04). Serum creatinine and PIIINP levels were increased [1.1 (0.9–1.3) mg/dL, and 5.8 (5.4–7.6)] μg/L, respectively), while urinary cGMP was reduced [270 (250–355) vs 581 (437–698) pmol/mL] in LKDs. No LKD developed cardiovascular or renal events during follow-up.Conclusions
Long-term kidney donors have no apparent structural myocardial abnormalities as assessed by contrast enhanced CMR. However, myocardial deformation of the apical segments, as well as apical rotation, and LV torsion are reduced. The concomitant increase in circulating PIIINP level is suggestive of fibrosis. Further studies, focused on US and EU patients are warranted to evaluate whether these early functional modifications will progress to a more compromised cardiac function and structure at a later time. 相似文献62.
Andrei Belitski Stefano Panzeri Cesare Magri Nikos K. Logothetis Christoph Kayser 《Journal of computational neuroscience》2010,29(3):533-545
Studies analyzing sensory cortical processing or trying to decode brain activity often rely on a combination of different
electrophysiological signals, such as local field potentials (LFPs) and spiking activity. Understanding the relation between
these signals and sensory stimuli and between different components of these signals is hence of great interest. We here provide
an analysis of LFPs and spiking activity recorded from visual and auditory cortex during stimulation with natural stimuli.
In particular, we focus on the time scales on which different components of these signals are informative about the stimulus,
and on the dependencies between different components of these signals. Addressing the first question, we find that stimulus
information in low frequency bands (<12 Hz) is high, regardless of whether their energy is computed at the scale of milliseconds
or seconds. Stimulus information in higher bands (>50 Hz), in contrast, is scale dependent, and is larger when the energy
is averaged over several hundreds of milliseconds. Indeed, combined analysis of signal reliability and information revealed
that the energy of slow LFP fluctuations is well related to the stimulus even when considering individual or few cycles, while
the energy of fast LFP oscillations carries information only when averaged over many cycles. Addressing the second question,
we find that stimulus information in different LFP bands, and in different LFP bands and spiking activity, is largely independent
regardless of time scale or sensory system. Taken together, these findings suggest that different LFP bands represent dynamic
natural stimuli on distinct time scales and together provide a potentially rich source of information for sensory processing
or decoding brain activity. 相似文献
63.
Lorusso A Covino C Priori G Bachi A Meldolesi J Chieregatti E 《The EMBO journal》2006,25(23):5443-5456
Enlargeosomes are small cytoplasmic vesicles that undergo rapid, Ca2+-dependent exo/endocytosis. The role of the cytoskeleton in these processes was unknown. In PC12-27 cells, microtubule disassembly had little effect on enlargeosomes, whereas microfilament disassembly increased markedly both their resting and stimulated exocytosis, and inhibited their endocytosis. Even at rest enlargeosomes are coated at their cytosolic surface by an actin-associated protein, annexin2, bound by a dual, Ca2+-dependent and Ca2+-independent mechanism. In contrast, the other enlargeosome marker, desmoyokin/Ahnak, is transported across the organelle membrane, apparently by an ABC transporter, and binds to its lumenal face. Annexin2-GFP expression revealed that, upon stimulation, the slow and random enlargeosome movement increases markedly and becomes oriented toward the plasma membrane. After annexin2 downregulation enlargeosome exocytosis induced by both [Ca2+]i rise and cytoskeleton disruption is inhibited, and the NGF-induced differentiation is blocked. Binding of annexin2 to the enlargeosome membrane, the most extensive ever reported (>50% annexin2 bound to approximately 3% of total membrane area), seems therefore to participate in the regulation of their exocytosis. 相似文献
64.
Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment 总被引:13,自引:0,他引:13
Sacchetti B Funari A Michienzi S Di Cesare S Piersanti S Saggio I Tagliafico E Ferrari S Robey PG Riminucci M Bianco P 《Cell》2007,131(2):324-336
The identity of cells that establish the hematopoietic microenvironment (HME) in human bone marrow (BM), and of clonogenic skeletal progenitors found in BM stroma, has long remained elusive. We show that MCAM/CD146-expressing, subendothelial cells in human BM stroma are capable of transferring, upon transplantation, the HME to heterotopic sites, coincident with the establishment of identical subendothelial cells within a miniature bone organ. Establishment of subendothelial stromal cells in developing heterotopic BM in vivo occurs via specific, dynamic interactions with developing sinusoids. Subendothelial stromal cells residing on the sinusoidal wall are major producers of Angiopoietin-1 (a pivotal molecule of the HSC "niche" involved in vascular remodeling). Our data reveal the functional relationships between establishment of the HME in vivo, establishment of skeletal progenitors in BM sinusoids, and angiogenesis. 相似文献
65.
Calabrese V Mancuso C Ravagna A Perluigi M Cini C De Marco C Butterfield DA Stella AM 《Journal of neurochemistry》2007,101(3):709-717
Increasing evidence suggests a critical role for oxidative and nitrosative stress in the pathogenesis of most important neurodegenerative disorders. Parkinson's disease (PD) is a neurodegenerative disease characterized by a severe depletion in number of dopaminergic cells of the substantia nigra (SN). Administration of L-DOPA (LD) is the more effective treatment for patients with PD. However, the vast majority of patients suffer LD-related complications, which represent the major problem in the clinical management of PD. In the present study, LD administration to rats resulted in a significant dose-dependent increase in Hsp70 synthesis which was specific for the SN. The amount of 70 kDa protein increased after 6 h treatment reaching the maximal induction after 24-48 h. Induction of Hsp70 in the SN was associated with a significant increase in constitutive Hsc70 and mitochondrial Hsp60 stress proteins, and with increased expression of mitochondrial complex I whereas no significant changes were found in the activity of complex IV. In the same experimental conditions, a significant decrease in reduced glutathione was observed, which was associated with an increased content of oxidized glutathione content as well as nitric oxide (NO) synthase activity, NO metabolites and nitrotyrosine immunoreactivity. Interestingly, Hsp70 induction, iNOS up-regulation and nitrotyrosine formation have been confirmed also in SN and striatum of rats treated with LD and carbidopa, this latter being an inhibitor of the peripheral DOPA decarboxylase. Our data are in favor of the importance of the heat shock signal pathway as a basic mechanism of defense against neurotoxicity elicited by free radical oxygen and nitrogen species produced in aging and neurodegenerative disorders. 相似文献
66.
Galli U Oliaro-Bosso S Taramino S Venegoni S Pastore E Tron GC Balliano G Viola F Sorba G 《Bioorganic & medicinal chemistry letters》2007,17(1):220-224
New dimethylamino truncated squalene ether derivatives containing a different aromatic moiety (phenyl, naphthyl, and biphenyl) or a simple alkyl (n-hexylic) group were synthesized as inhibitors of the oxidosqualene cyclase (OSC) and of the sterol biosynthetic pathway. The activity against human OSC was compared with the activity against the OSCs of pathogenic organisms such as Pneumocystis carinii and Trypanosoma cruzi. The phenyl derivative was the most potent inhibitor of T. cruzi OSC. 相似文献
67.
MicroRNA-133 controls cardiac hypertrophy 总被引:23,自引:0,他引:23
68.
Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state 总被引:2,自引:0,他引:2
Brown BD Gentner B Cantore A Colleoni S Amendola M Zingale A Baccarini A Lazzari G Galli C Naldini L 《Nature biotechnology》2007,25(12):1457-1467
We have shown previously that transgene expression can be suppressed in hematopoietic cells using vectors that are responsive to microRNA (miRNA) regulation. Here we investigate the potential of this approach for more sophisticated control of transgene expression. Analysis of the relationship between miRNA expression levels and target mRNA suppression suggested that suppression depends on a threshold miRNA concentration. Using this information, we generated vectors that rapidly adjust transgene expression in response to changes in miRNA expression. These vectors sharply segregated transgene expression between closely related states of therapeutically relevant cells, including dendritic cells, hematopoietic and embryonic stem cells, and their progeny, allowing positive/negative selection according to the cells' differentiation state. Moreover, two miRNA target sites were combined to restrict transgene expression to a specific cell type in the liver. Notably, the vectors did not detectably perturb endogenous miRNA expression or regulation of natural targets. The properties of miRNA-regulated vectors should allow for safer and more effective therapeutic applications. 相似文献
69.
A New Medical Device Rigeneracons Allows to Obtain Viable Micro‐Grafts From Mechanical Disaggregation of Human Tissues 下载免费PDF全文
70.
C D'Aniello A Fico L Casalino O Guardiola G Di Napoli F Cermola D De Cesare R Tatè G Cobellis E J Patriarca G Minchiotti 《Cell death and differentiation》2015,22(7):1094-1105
Increasing evidence indicates that metabolism is implicated in the control of stem cell identity. Here, we demonstrate that embryonic stem cell (ESC) behaviour relies on a feedback loop that involves the non-essential amino acid L-Proline (L-Pro) in the modulation of the Gcn2-Eif2α-Atf4 amino acid starvation response (AAR) pathway that in turn regulates L-Pro biosynthesis. This regulatory loop generates a highly specific intrinsic shortage of L-Pro that restricts proliferation of tightly packed domed-like ESC colonies and safeguards ESC identity. Indeed, alleviation of this nutrient stress condition by exogenously provided L-Pro induces proliferation and modifies the ESC phenotypic and molecular identity towards that of mesenchymal-like, invasive pluripotent stem cells. Either pharmacological inhibition of the prolyl-tRNA synthetase by halofuginone or forced expression of Atf4 antagonises the effects of exogenous L-Pro. Our data provide unprecedented evidence that L-Pro metabolism and the nutrient stress response are functionally integrated to maintain ESC identity.Naturally occurring amino acids are emerging as key players in the regulation of the phenotypic plasticity of stem cells.1, 2, 3, 4, 5 Indeed, exogenously provided threonine and methionine, two essential amino acids (EAAs), regulate self-renewal and differentiation of pluripotent stem cells.2 Moreover, exogenously provided L-Proline (L-Pro), a non-essential amino acid (NEAA), induces mouse ESCs towards an embryonic stem cell-to-mesenchymal-like transition (esMT) that converts compact, adherent ESCs into mesenchymal-like spindle-shaped, highly invasive and metastatic pluripotent stem cells.4 This fully reversible process resembles the epithelial-to-mesenchymal transition (EMT), which is essential for normal development and contributes to pathological cancer progression.6, 7, 8 Interestingly, the Aldh18a1 gene is specifically induced in and marks the Primitive Endoderm (PrE) in the time window when the pluripotent epiblast precursors are specified within the inner cell mass (ICM) of the blastocyst.9 Since the Aldh18a1 enzyme catalyses the first and rate-limiting step of L-Pro biosynthesis, these findings suggest that L-Pro metabolism may regulate cell lineage segregation in early mammalian embryos. Despite its relevance, the molecular mechanisms underlying L-Pro control of stem cell identity remain largely unknown. This prompted us to investigate the early molecular events regulated by exogenously provided L-Pro in mouse ESCs. 相似文献