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771.
The novel PKCθ isoform is highly expressed in T-cells, brain and skeletal muscle and originally thought to have a restricted distribution. It has been extensively studied in T-cells and shown to be important for apoptosis, T-cell activation and proliferation. Recent studies showed its presence in other tissues and importance in insulin signaling, lung surfactant secretion, intestinal barrier permeability, platelet and mast-cell functions. However, little information is available for PKCθ activation by gastrointestinal (GI) hormones/neurotransmitters and growth factors. In the present study we used rat pancreatic acinar cells to explore their ability to activate PKCθ and the possible interactions with important cellular mediators of their actions. Particular attention was paid to cholecystokinin (CCK), a physiological regulator of pancreatic function and important in pathological processes affecting acinar function, like pancreatitis. PKCθ-protein/mRNA was present in the pancreatic acini, and T538-PKCθ phosphorylation/activation was stimulated only by hormones/neurotransmitters activating phospholipase C. PKCθ was activated in time- and dose-related manner by CCK, mediated 30% by high-affinity CCK(A)-receptor activation. CCK stimulated PKCθ translocation from cytosol to membrane. PKCθ inhibition (by pseudostrate-inhibitor or dominant negative) inhibited CCK- and TPA-stimulation of PKD, Src, RafC, PYK2, p125(FAK) and IKKα/β, but not basal/stimulated enzyme secretion. Also CCK- and TPA-induced PKCθ activation produced an increment in PKCθ's direct association with AKT, RafA, RafC and Lyn. These results show for the first time the PKCθ presence in pancreatic acinar cells, its activation by some GI hormones/neurotransmitters and involvement in important cell signaling pathways mediating physiological responses (enzyme secretion, proliferation, apoptosis, cytokine expression, and pathological responses like pancreatitis and cancer growth). 相似文献
772.
PMP1, a regulatory subunit of the yeast plasma membrane H+-ATPase, is a single transmembrane helix protein. Its cytoplasmic C-terminus possesses several positively charged residues and interacts with phosphatidylserine lipids as shown through both 1H- and 2H-NMR experiments. We used all-atom molecular dynamics simulations to obtain atomic-scale data on the effects of membrane interface lipid composition on PMP1 structure and tilt. PMP1 was embedded in two hydrated bilayers, differing in the composition of the interfacial region. The neutral bilayer is composed of POPC (1-palmitoyl-2-oleoyl-3-glycero-phosphatidylcholine) lipids and the negatively charged bilayer is composed of POPC and anionic POPS (1-palmitoyl-2-oleoyl-3-glycero-phosphatidylserine) lipids. Our results were consistent with NMR data obtained previously, such as a lipid sn-2 chain lying on the W28 aromatic ring and in the groove formed on one side of the PMP1 helix. In pure POPC, the transmembrane helix is two residues longer than the initial structure and the helix tilt remains constant at 6 ± 3°. By contrast, in mixed POPC-POPS, the initial helical structure of PMP1 is stable throughout the simulation time even though the C-terminal residues interact strongly with POPS headgroups, leading to a significant increase of the helix tilt within the membrane to 20 ± 5°. 相似文献
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Maria Lpez‐Aizpún Claire A. Horrocks Alice F. Charteris Karina A. Marsden Veronica S. Ciganda Jess R. Evans David R. Chadwick Laura M. Crdenas 《Global Change Biology》2020,26(4):2002-2013
Nitrous oxide (N2O) is an air pollutant of major environmental concern, with agriculture representing 60% of anthropogenic global N2O emissions. Much of the N2O emissions from livestock production systems result from transformation of N deposited to soil within animal excreta. There exists a substantial body of literature on urine patch N2O dynamics, we aimed to identify key controlling factors influencing N2O emissions and to aid understanding of knowledge gaps to improve GHG reporting and prioritize future research. We conducted an extensive literature review and random effect meta‐analysis (using REML) of results to identify key relationships between multiple potential independent factors and global N2O emissions factors (EFs) from urine patches. Mean air temperature, soil pH and ruminant animal species (sheep or cow) were significant factors influencing the EFs reviewed. However, several factors that are known to influence N2O emissions, such as animal diet and urine composition, could not be considered due to the lack of reported data. The review highlighted a widespread tendency for inadequate metadata and uncertainty reporting in the published studies, as well as the limited geographical extent of investigations, which are more often conducted in temperate regions thus far. Therefore, here we give recommendations for factors that are likely to affect the EFs and should be included in all future studies, these include the following: soil pH and texture; experimental set‐up; direct measurement of soil moisture and temperature during the study period; amount and composition of urine applied; animal type and diet; N2O emissions with a measure of uncertainty; data from a control with zero‐N application and meteorological data. 相似文献
776.
Alaa M. H. El-Bitar Moustafa Sarhan Mohamed A. Abdel-Rahman Veronica Quintero-Hernandez Chie Aoki-Utsubo Mohsen A. Moustafa Lourival D. Possani Hak Hotta 《International journal of peptide research and therapeutics》2020,26(2):811-821
Growing global viral infections have been a serious public health problem in recent years. This current situation emphasizes the importance of developing m 相似文献
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Paolo Palma Maria Luisa Romiti Carla Montesano Veronica Santilli Nadia Mora Angela Aquilani Stefania Dispinseri Hyppolite K. Tchidjou Marco Montano Lars E. Eriksson Stefania Baldassari Stefania Bernardi Gabriella Scarlatti Britta Wahren Paolo Rossi 《PloS one》2013,8(11)
Subjects
Twenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm3.Intervention
Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96.Results
Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A.Conclusions
The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population.Trial registration
clinicaltrialsregister.eu _2007-002359-18 IT 相似文献779.
Chunmei Yang Heehyoung Lee Veronica Jove Jiehui Deng Wang Zhang Xueli Liu Stephen Forman Thanh H. Dellinger Mark Wakabayashi Hua Yu Sumanta Pal 《PloS one》2013,8(1)
Background
Several previous studies have identified a strong association between T-cell infiltration and clinical outcome in ovarian cancer. The role of B-cells remains controversial, however.Methods
Forty-nine paraffin-embedded omental specimens derived from patients with high grade epithelial ovarian cancer were assessed. Immunohistochemical analyses were performed to characterize expression of CD19+ B-cells and pSTAT3 as high (>50% positively staining cells [PSCs]) or low (<50% PSCs). The Kaplan-Meier method with log-rank test was used to determine the association between clinicopathologic parameters and overall survival (OS). A multi-variate Cox proportional hazards regression analysis including nature of debulking (primary vs secondary), histology, tumor grade, receipt of prior chemotherapy, B-cell infiltration and pSTAT3 expression was performed.Results
Median OS was 160.6 months in those patients with low B-cell expression vs 47.3 months in those with high B-cell expression (P = 0.0015). Similarly, median OS was improved in those patients with low pSTAT3 expression (160.6 vs 47.9 months, P = 0.02). In a multivariate model to predict survival, only the degree of B-cell infiltration and clinical stage were retained. pSTAT3 expression did not enter the final model, possibly be due to a high positive correlation with B-cell infiltration (r = 0.82, P<0.0001).Conclusions
Increased B-cell infiltration and pSTAT3 expression in omental tissue are associated with poorer survival. 相似文献780.
Nicola Sverzellati Davide Colombi Giorgia Randi Antonio Pavarani Mario Silva Simon L. Walsh Massimo Pistolesi Veronica Alfieri Alfredo Chetta Mauro Vaccarezza Marco Vitale Ugo Pastorino 《PloS one》2013,8(7)