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221.
Garlanda C Di Liberto D Vecchi A La Manna MP Buracchi C Caccamo N Salerno A Dieli F Mantovani A 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(5):3119-3125
Toll IL-1R 8/single Ig IL-1-related receptor (TIR8/SIGIRR) is a member of the IL-1R family, expressed by epithelial tissues and immature dendritic cells, and is regarded as a negative regulator of TLR/IL-1R signaling. Tir8-deficient mice were rapidly killed by intranasal administration of low doses of Mycobacterium tuberculosis, despite controlling efficiently the number of viable bacilli in different organs. Tir8(-/-)-infected mice showed an increased number of neutrophils and macrophages in the lungs; however, mycobacteria-specific CD4 and CD8 T cells were similar in Tir8(-/-) and Tir8(+/+) mice. Exaggerated mortality of Tir8(-/-) mice was due to massive liver necrosis and was accompanied by increased levels of IL-1beta and TNF-alpha in lung mononuclear cells and serum, as well as by increased production of IL-1beta and TNF-alpha by M. tuberculosis-infected dendritic cells in vitro. Accordingly, blocking IL-1beta and TNF-alpha with a mix of anti-cytokine Abs, significantly prolonged survival of Tir8(-/-) mice. Thus, TIR8/SIGIRR plays a key role in damping inflammation and tissue damage in M. tuberculosis infection. 相似文献
222.
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
223.
Caffeine and accumbens shell dopamine 总被引:2,自引:1,他引:1
It has been reported that caffeine (1.5-30 mg/kg i.p.) as well as specific A1 (DPCPX, 8-cyclopentyl-1,3-dipropylxanthine) receptor antagonists fail to increase extracellular dopamine (DA) in the shell of the nucleus accumbens (NAc). However, it has also been reported that caffeine (10 and 30 mg/kg i.p.) and the A1 antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) increases NAc shell DA. To clarify this issue rats were implanted with microdialysis probes at different sites in the NAc shell, in the medial prefrontal cortex (PFCX, infralimbic cortex), and at the border between those areas. Irrespective of probe placement within the NAc shell and of the use of different surgical anesthetics (chloral hydrate and ketamine), we failed to observe changes in dialysate DA after 10 and 30 mg/kg i.p. of caffeine. Similarly negative results were obtained with DPCPX and CPFPX, two potent and selective A1 receptor antagonists. A significant increase of DA was obtained after caffeine when probes were located at the border between the NAc shell and the PFCX (10 and 30 mg/kg) or in the PFCX (10 mg/kg). In view of this and of our previous report that caffeine increases dialysate DA in the medial PFCX, we conclude that the increase in dialysate DA by caffeine observed by others arises from the medial PFCX rather than from the NAc shell as a result of placement of microdialysis probes at the border between the NAc shell and the PFCX. 相似文献
224.
Identification of differentially expressed microRNAs by microarray: a possible role for microRNA genes in pituitary adenomas 总被引:11,自引:0,他引:11
Bottoni A Zatelli MC Ferracin M Tagliati F Piccin D Vignali C Calin GA Negrini M Croce CM Degli Uberti EC 《Journal of cellular physiology》2007,210(2):370-377
MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by targeting mRNA. It has been demonstrated that miRNA expression is altered in many human cancers, suggesting that they may play a role in human neoplasia. To determine whether miRNA expression is altered in pituitary adenomas, we analyzed the entire miRNAome in 32 pituitary adenomas and in 6 normal pituitary samples by microarray and by Real-Time PCR. Here, we show that 30 miRNAs are differentially expressed between normal pituitary and pituitary adenomas. Moreover, 24 miRNAs were identified as a predictive signature of pituitary adenoma and 29 miRNAs were able to predict pituitary adenoma histotype. miRNA expression could differentiate micro- from macro-adenomas and treated from non-treated patient samples. Several of the identified miRNAs are involved in cell proliferation and apoptosis, suggesting that their deregulated expression may be involved in pituitary tumorigenesis. Predictive miRNAs could be potentially useful diagnostic markers, improving the classification of pituitary adenomas. 相似文献
225.
Parmiani G De Filippo A Novellino L Castelli C 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(4):1975-1979
The individual, unique tumor Ags, which characterize each single tumor, were described 50 years ago in rodents but their molecular characterization was limited to few of them and obtained during the last 20 years. Here we summarize the evidence for the existence and the biological role of such Ags in human tumors, although such evidence was provided only during the last 10 years and by a limited number of studies, a fact leading to a misrepresentation of unique Ags in human tumor immunology. This was also due to the increasing knowledge on the shared, self-human tumor Ags, which have been extensively used as cancer vaccines. In this review, we highlight the biological and clinical importance of unique Ags and suggest how they could be used in clinical studies aimed at assessing their immunogenic and clinical potential both in active and adoptive immunotherapy of human tumors. 相似文献
226.
Biogenesis and recycling of synaptic vesicles are accompanied by sorting processes that preserve the molecular composition of the compartments involved. In the present study, we have addressed the targeting of synaptobrevin 2/VAMP2 (vesicle-associated membrane protein 2), a critical component of the synaptic vesicle--fusion machinery, in a heterotypic context where its sorting is not confounded by the presence of other neuron-specific molecules. Ectopically expressed synaptophysin I interacts with VAMP2 and alters its default surface targeting to a prominent vesicular distribution, with no effect on the targeting of other membrane proteins. Protein-protein interaction is not sufficient for the control of VAMP2 sorting, which is mediated by the C-terminal domain of synaptophysin I. Synaptophysin I directs the sorting of VAMP2 to vesicles before surface delivery, without influencing VAMP2 endocytosis. Consistent with this, dynamin and alpha-SNAP (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein) mutants which block trafficking at the plasma membrane do not abrogate the effect of synaptophysin I on VAMP2 sorting. These results indicate that the sorting determinants of synaptic vesicle proteins can operate independently of a neuronal context and implicate the association of VAMP2 with synaptophysin I in the specification of the pathway of synaptic vesicle biogenesis. 相似文献
227.
Pyriforms are ovarian follicle nurse cells that undergo apoptosis at the end of previtellogenesis and are completely eliminated
by the epithelium. This event is accompanied by the active transfer of organelles and macromolecules to the oocyte via an
intercellular bridge. Since it would be a nonsense for damaged mitochondria to reach the oocyte, we have postulated that pyriform
cells have adapted their apoptotic machinery to prevent mitochondrial degradation. To verify this hypothesis, we have studied
mitochondrial morphology and functionality during follicle cell regression. Cytological and biochemical evidence indicates
that mitochondria in pyriforms maintain their size, organization and membrane potential. This clearly indicates that they
are not involved in apoptosis signalling/progression. This block would favour both the oocyte, by increasing the pool of organelles
available from follicle cells, and also the regressing pyriforms, by maintaining the energy resources required for completion
of their nurse function. The block is probably attributable to an over-expression of Bcl-2 and might be carried out by sequestering
cytochrome c inside the organelles. As demonstrated by in vitro experiments, the mitochondrial apoptosis pathway can be activated
by stress induction, such as serum deprivation, but not following physiological pro-apoptotic signalling, such as treatment
with gonadotrophin-releasing hormone.
These studies were supported by a grant from the MIUR (PRIN project: Molecular responses of embryonic, differentiated and
tumoral cells exposed to cadmium intoxication). 相似文献
228.
Chiara Angelone 《Geobios》2007,40(3):407
A systematic revision of Italian Messinian Prolagus findings has been performed, evidencing the presence of four different species. Comparative analyses allowed their separation in two groups corresponding to two different palaeobioprovinces characterized by distinct faunal affinities, source areas and tempos and modes of colonization. Such considerations allowed to cast a new light on the palaeobiogeography and the migration pathways of continental vertebrate faunas in the Mediterranean area during Messinian, and to give a new importance to the genus Prolagus as a palaeobiogeographical marker. 相似文献
229.
Bacillus subtilis gene cluster involved in calcium carbonate biomineralization 总被引:2,自引:0,他引:2
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Barabesi C Galizzi A Mastromei G Rossi M Tamburini E Perito B 《Journal of bacteriology》2007,189(1):228-235
230.
de Tombe PP Belus A Piroddi N Scellini B Walker JS Martin AF Tesi C Poggesi C 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,292(3):R1129-R1136
We employed single myofibril techniques to test whether the presence of slow skeletal troponin-I (ssTnI) is sufficient to induce increased myofilament calcium sensitivity (EC(50)) and whether modulation of EC(50) affects the dynamics of force development. Studies were performed using rabbit psoas myofibrils activated by rapid solution switch and in which Tn was partially replaced for either recombinant cardiac Tn(cTn) or Tn composed of recombinant cTn-T (cTnT) and cTn-C (cTnC), and recombinant ssTnI (ssTnI-chimera Tn). Tn exchange was performed in rigor solution (0.5 mg/ml Tn; 20 degrees C; 2 h) and confirmed by SDS-PAGE. cTnI exchange induced a decrease in EC(50); ssTnI-chimera Tn exchange induced a further decrease in EC(50) (in microM: endogenous Tn, 1.35 +/- 0.08; cTnI, 1.04 +/- 0.13; ssTnI-chimera Tn, 0.47 +/- 0.03). EC(50) was also decreased by application of 100 microM bepridil (control: 2.04 +/- 0.03 microM; bepridil 1.35 +/- 0.03 microM). Maximum tension was not different between any groups. Despite marked alterations in EC(50), none of the dynamic activation-relaxation parameters were affected under any condition. Our results show that 1) incorporation of ssTnI into the fast skeletal sarcomere is sufficient to induce increased myofilament Ca(2+) sensitivity, and 2) the dynamics of actin-myosin interaction do not correlate with EC(50). This result suggests that intrinsic cross-bridge cycling rate is not altered by the dynamics of thin-filament activation. 相似文献