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Case-control sampling is popular in epidemiological research because of its cost and time saving. In a logistic regression model, with limited knowledge on the covariance matrix of the point estimator of the regression coefficients a priori, there exists no fixed sample size analysis. In this study, we propose a two-stage sequential analysis, in which the optimal sample fraction and the required sample size to achieve a predetermined volume of a joint confidence set are estimated in an interim analysis. Additionally required observations are collected in the second stage according to the estimated optimal sample fraction. At the end of the experiment, data from these two stages are combined and analyzed for statistical inference. Simulation studies are conducted to justify the proposed two-stage procedure and an example is presented for illustration. It is found that the proposed two-stage procedure performs adequately in the sense that the resultant joint confidence set has a well-controlled volume and achieves the required coverage probability. Furthermore, the optimal sample fractions among all the selected scenarios are close to one. Hence, the proposed procedure can be simplified by always considering a balance design. 相似文献
995.
Determination of oxidative metabolism in the brain using in vivo 13C NMR spectroscopy (13C MRS) typically requires repeated blood sampling throughout the study to measure blood glucose concentration and fractional
enrichment (input function). However, drawing blood from small animals, such as young rats, placed deep inside the magnet
is technically difficult due to their small total blood volume. In the present study, a custom-built animal holder enabled
temporary removal of the animal from the magnet for blood collection, followed by accurate repositioning in the exact presampling
position without degradation of B0 shimming. 13C label incorporation into glutamate C4 and C3 positions during a 120 min [1,6-13C2] glucose infusion was determined in 28-day-old rats (n = 4) under α-chloralose sedation using localized, direct-detected
in vivo 13C MRS at 9.4T. The tricarboxylic acid cycle activity rate (V
TCA) determined using a one-compartment metabolic modeling was 0.67 ± 0.13 μmol/g/min, a value comparable to previous ex vivo
studies. This methodology opens the avenue for in vivo measurements of brain metabolic rates using 13C MRS in small animals. 相似文献
996.
Post-conflict behaviour has been widely investigated in anthropoid primates but not extensively in prosimians. Here, we report
the reconciliation pattern of a 14-individual group of wild brown lemurs (Eulemur fulvus) in the Berenty gallery forest (South Madagascar). We found that reconciliation occurs only in the non-feeding context and
that it works in reducing the risk of renewed aggression. Thus, reconciliation would provide an immediate positive feedback
that is probably independent of the quality of the relationship between opponents. Reconciliation may also be a hic-et-nunc
mechanism, needed to avoid conflict spreading across group members, possibly leading to social disruption. 相似文献
997.
Zhao D Young JS Chen YH Shen E Yi T Todorov I Chu PG Forman SJ Zeng D 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(2):856-868
Chronic graft-versus-host disease (cGVHD) is considered an autoimmune-like disease mediated by donor CD4(+) T cells, but the origin of the autoreactive T cells is still controversial. In this article, we report that the transplantation of DBA/2 donor spleen cells into thymectomized MHC-matched allogeneic BALB/c recipients induced autoimmune-like cGVHD, although not in control syngeneic DBA/2 recipients. The donor-type CD4(+) T cells from the former but not the latter recipients induced autoimmune-like manifestations in secondary allogeneic BALB/c as well as syngeneic DBA/2 recipients. Transfer of donor-type CD4(+) T cells from secondary DBA/2 recipients with disease into syngeneic donor-type or allogeneic host-type tertiary recipients propagated autoimmune-like manifestations in both. Furthermore, TCR spectratyping revealed that the clonal expansion of the autoreactive CD4(+) T cells in cGVHD recipients was initiated by an alloimmune response. Finally, hybridoma CD4(+) T clones derived from DBA/2 recipients with disease proliferated similarly in response to stimulation by syngeneic donor-type or allogeneic host-type dendritic cells. These results demonstrate that the autoimmune-like manifestations in cGVHD can be mediated by a population of donor CD4(+) T cells in transplants that simultaneously recognize Ags presented by both donor and host APCs. 相似文献
998.
Alfaro C Perez-Gracia JL Suarez N Rodriguez J Fernandez de Sanmamed M Sangro B Martin-Algarra S Calvo A Redrado M Agliano A Gonzalez A Rodriguez I Bolaños E Hervás-Stubbs S Perez-Calvo J Benito A Peñuelas I Vigil C Richter J Martinez-Forero I Melero I 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(11):6130-6142
Twenty-four patients with metastatic cancer received two cycles of four daily immunizations with monocyte-derived dendritic cells (DC). DC were incubated with preheated autologous tumor lysate and subsequently with IFN-α, TNF-α, and polyinosinic:polycytidylic acid to attain type 1 maturation. One DC dose was delivered intranodally, under ultrasound control, and the rest intradermally in the opposite thigh. Cyclophosphamide (day -7), GM-CSF (days 1-4), and pegIFN alpha-2a (days 1 and 8) completed each treatment cycle. Pretreatment with cyclophosphamide decreased regulatory T cells to levels observed in healthy subjects both in terms of percentage and in absolute counts in peripheral blood. Treatment induced sustained elevations of IL-12 in serum that correlated with the output of IL-12p70 from cultured DC from each individual. NK activity in peripheral blood was increased and also correlated with the serum concentration of IL-12p70 in each patient. Circulating endothelial cells decreased in 17 of 18 patients, and circulating tumor cells markedly dropped in 6 of 19 cases. IFN-γ-ELISPOT responses to DC plus tumor lysate were observed in 4 of 11 evaluated cases. Tracing DC migration with [(111)In] scintigraphy showed that intranodal injections reached deeper lymphatic chains in 61% of patients, whereas with intradermal injections a small fraction of injected DC was almost constantly shown to reach draining inguinal lymph nodes. Five patients experienced disease stabilization, but no objective responses were documented. This combinatorial immunotherapy strategy is safe and feasible, and its immunobiological effects suggest potential activity in patients with minimal residual disease. A randomized trial exploring this hypothesis is currently ongoing. 相似文献
999.
Ajdžanović V Spasojević I Sošić-Jurjević B Filipović B Trifunović S Sekulić M Milošević V 《The Journal of membrane biology》2011,239(3):131-135
A decrease of erythrocyte membrane fluidity can contribute to the pathophysiology of hypertension. Soy products, which are
used as alternative therapeutics in some cardiovascular conditions, contain various isoflavones (genistein, daidzein, and
their glucosides, genistin and daidzin), which can incorporate cellular membrane and change its fluidity. The aim of this
study was to examine the effects of soy extract (which generally corresponds to the soy products of isoflavone composition)
on erythrocyte membrane fluidity at graded depths. We used electron paramagnetic resonance spectroscopy and fatty acid spin
probes (5-DS and 12-DS), the spectra of which are dependent on membrane fluidity. After being treated with soy extract, erythrocytes
showed a significant (P = 0.016) decrease of membrane fluidity near the hydrophilic surface, while there were no significant changes of fluidity
in deeper hydrophobic membrane regions. These results suggest that soy products containing high levels of genistein and isoflavone
glucosides may not be suitable for use in hypertension because they decrease erythrocyte membrane fluidity. 相似文献
1000.
Bosanac I Phu L Pan B Zilberleyb I Maurer B Dixit VM Hymowitz SG Kirkpatrick DS 《Journal of molecular biology》2011,408(3):420-3071
Ubiquitination refers to the covalent addition of ubiquitin (Ub) to substrate proteins or other Ub molecules via the sequential action of three enzymes (E1, E2, and E3). Recent advances in mass spectrometry proteomics have made it possible to identify and quantify Ub linkages in biochemical and cellular systems. We used these tools to probe the mechanisms controlling linkage specificity for UbcH5A. UbcH5A is a promiscuous E2 enzyme with an innate preference for forming polyubiquitin chains through lysine 11 (K11), lysine 48 (K48), and lysine 63 (K63) of Ub. We present the crystal structure of a noncovalent complex between Ub and UbcH5A. This structure reveals an interaction between the Ub surface flanking K11 and residues adjacent to the E2 catalytic cysteine and suggests a possible role for this surface in formation of K11 linkages. Structure-guided mutagenesis, in vitro ubiquitination and quantitative mass spectrometry have been used to characterize the ability of residues in the vicinity of the E2 active site to direct synthesis of K11- and K63-linked polyubiquitin. Mutation of critical residues in the interface modulated the linkage specificity of UbcH5A, resulting in generation of more K63-linked chains at the expense of K11-linkage synthesis. This study provides direct evidence that the linkage specificity of E2 enzymes may be altered through active-site mutagenesis. 相似文献