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51.
Geraldine H. Fleming Catherine M. Kramer Trang Le Raymond D. Shillito 《Plant science》1995,110(2):187-192
During eukaryotic cell transformation, the transforming DNA must enter the host cell, traverse the cytoplasm and enter the nucleus before becoming stably integrated into the genome. The limiting step for plant protoplast transformation may lie at the cell membrane, the nuclear membrane, or at the integration step. We show here that the size of the DNA fragment containing the selectable marker used to monitor transformation can directly affect the efficiency of stable transformation. In both tobacco and maize protoplasts, the smallest DNA fragments gave the highest stable transformation frequencies. 相似文献
52.
Bianca Altvater Silke Landmeier Sibylle Pscherer Jaane Temme Heribert Juergens Martin Pule Claudia Rossig 《Cancer immunology, immunotherapy : CII》2009,58(12):1991-2001
Regulatory NK cell receptors can contribute to antigen-specific adaptive immune responses by modulating T cell receptor (TCR)-induced
T cell activation. We investigated the potential of the NK cell receptor 2B4 (CD244) to enhance tumor antigen-induced activation
of human T cells. 2B4 is a member of the CD2 receptor subfamily with both activating and inhibitory functions in NK cells.
In T cells, its expression is positively associated with the acquisition of a cytolytic effector memory phenotype. Recombinant
chimeric receptors that link extracellular single-chain Fv fragments specific for the tumor-associated surface antigens CD19
and GD2 to the signaling domains of human 2B4 and/or TCRζ were expressed in non-specifically activated peripheral blood T cells by
retroviral gene transfer. While 2B4 signaling alone failed to induce T cell effector functions or proliferation, it significantly
augmented the antigen-specific activation responses induced by TCRζ. 2B4 costimulation did not affect the predominant effector
memory phenotype of expanding T cells, nor did it increase the proportion of T cells with regulatory phenotype (CD4+CD25hiFoxP3+). These data support a costimulatory role for 2B4 in human T cell subpopulations. As an amplifier of TCR-mediated signals,
2B4 may provide a powerful new tool for immunotherapy of cancer, promoting sustained activation and proliferation of gene-modified
antitumor T cells. 相似文献
53.
Efficacy of three‐in‐one capsule bismuth quadruple therapy for Helicobacter pylori eradication in clinical practice in a multinational patient population 下载免费PDF全文
54.
The Allee effect can result in a negative population growth rate at low population density. Consequently, populations below
a minimum (critical) density are unlikely to persist. A lower limit on population size should constrain the loss of genetic
variability due to genetic drift during population bottlenecks or founder events. We explored this phenomenon by modeling
changes in genetic variability and differentiation during simulated bottlenecks of the alpine copepod, Hesperodiaptomus shoshone. Lake surveys, whole-lake re-introduction experiments and model calculations all indicate that H. shoshone should be unlikely to establish or persist at densities less than 0.5–5 individuals m−3. We estimated the corresponding range in minimum effective population size using the distribution of habitat (lake) sizes
in nature and used these values to model the expected heterozygosity, allelic richness and genetic differentiation resulting
from population bottlenecks. We found that during realistic bottlenecks or founder events, >90% of H. shoshone populations in the Sierra Nevada may be resistant to significant changes in heterozygosity or genetic distance, and 70–75%
of populations may lose <10% of allelic richness. We suggest that ecological constraints on minimum population size be considered
when using genetic markers to estimate historical population dynamics. 相似文献
55.
Uluçkan O Eagleton MC Floyd DH Morgan EA Hirbe AC Kramer M Dowland N Prior JL Piwnica-Worms D Jeong SS Chen R Weilbaecher K 《Journal of cellular biochemistry》2008,104(4):1311-1323
Platelets contribute to the development of metastasis, the most common cause of mortality in cancer patients, but the precise role that anti-platelet drugs play in cancer treatment is not defined. Metastatic tumor cells can produce platelet alphaIIb beta3 activators, such as ADP and thromboxane A(2) (TXA(2)). Inhibitors of platelet beta3 integrins decrease bone metastases in mice but are associated with significant bleeding. We examined the role of a novel soluble apyrase/ADPase, APT102, and an inhibitor of TXA(2) synthesis, acetylsalicylic acid (aspirin or ASA), in mouse models of experimental bone metastases. We found that treatment with ASA and APT102 in combination (ASA + APT102), but not either drug alone, significantly decreased breast cancer and melanoma bone metastases in mice with fewer bleeding complications than observed with alphaIIb beta3 inhibition. ASA + APT102 diminished tumor cell induced platelet aggregation but did not directly alter tumor cell viability. Notably, APT102 + ASA treatment did not affect initial tumor cell distribution and similar results were observed in beta3-/- mice. These results show that treatment with ASA + APT102 decreases bone metastases without significant bleeding complications. Anti-platelet drugs such as ASA + APT102 could be valuable experimental tools for studying the role of platelet activation in metastasis as well as a therapeutic option for the prevention of bone metastases. 相似文献
56.
Estrogenic effect on swelling and monocytic receptor expression in an arthritic temporomandibular joint model 总被引:1,自引:0,他引:1
Guan G Kerins CC Bellinger LL Kramer PR 《The Journal of steroid biochemistry and molecular biology》2005,97(3):241-250
Clinical presentation of temporomandibular joint (TMJ) disorders are more common in women and changes in the female hormone estrogen affect the level of swelling, pro-inflammatory cytokine release and pain in animal models of TMJ arthritis. Estrogen also modulates the expression of the CD16 receptor in vitro. This alters pro-inflammatory cytokine release in monocytes/macrophages when auto-antigens and arthritic factors bind the CD16 receptor. This study investigated the effects of various levels of estrogen on the intensity of inflammation and CD16 expression in a TMJ arthritic animal model. The experiments included rats that were intact or ovariectomized (OVX), eliminating the major source of estrogen output. A portion of the OVX animals had estrogen replaced with 17-beta estradiol (E2) using Alzet pumps. In OVX animals E2 levels were administered for 10 days to create an artificial estrus cycle or to simulate pregnancy. Following E2 treatment the rats were given an intra-articular TMJ injection of saline or complete Freund's adjuvant (CFA). CFA injection significantly increased TMJ swelling, stress induced chromodacryorrhea and attenuated food intake, thus indicating the adjuvant induced TMJ pain/inflammation. Removing endogenous E2 through OVX reduced CFA induced TMJ inflammation, whereas CFA increased the number of TMJ monocytes expressing the CD14 receptor equally in all groups irrespective of plasma E2 levels. Paradoxically, higher levels of E2 reduced the number of TNF-alpha positive, CD16+ and double labeled CD14+/CD16+ cells. The findings indicate that reduced plasma E2 levels attenuated CFA induced TMJ inflammation, whereas increasing E2 levels enhanced TMJ swelling in a dose dependent manner. Estrogenic group differences in CFA induced swelling were independent of TMJ CD14+, CD14+/CD16+ or CD16+ cell numbers suggesting E2 action on the CFA immune response primarily excluded CD16 receptor action. 相似文献
57.
Isolation and partial characterization of an Mr 60,000 subunit of a type 2A phosphatase from rabbit reticulocytes 总被引:12,自引:0,他引:12
A Mr 60,000 peptide that modulates the activity of the Mr 35,000 catalytic subunit of a type 2A phosphatase has been isolated from rabbit reticulocytes and partially characterized. The peptide appears to be a subunit of the intact phosphatase that has been isolated under nondenaturing conditions. The Mr 60,000 peptide itself is catalytically inactive. However, it binds to the Mr 35,000 catalytic subunit causing a decrease in its activity for dephosphorylation of phosphorylated 40 S ribosomal subunits, but an increase in dephosphorylation of peptide initiation factor 2 phosphorylated in its alpha subunit. Reassociation of the Mr 60,000 and the Mr 35,000 peptides yields a two-subunit phosphatase with a Stokes radius of 42 A; sedimentation coefficient, S20,w of 5.1 S; molecular weight of 89,000. These parameters are compared to those of the native three-subunit enzyme and those of the isolated Mr 35,000 and 60,000 peptides. 相似文献
58.
Bianca Sylvester Dana-Maria Muntean Laurian Vlase Lavinia Lupuţ Emilia Licarete 《Journal of liposome research》2018,28(1):49-61
Quality by design principles (QbD) were used to assist the formulation of prednisolone-loaded long-circulating liposomes (LCL-PLP) in order to gain a more comprehensive understanding of the preparation process. This approach enables us to improve the final product quality in terms of liposomal drug concentration, encapsulation efficiency and size, and to minimize preparation variability. A 19-run D-optimal experimental design was used to study the impact of the highest risk factors on PLP liposomal concentration (Y1- μg/ml), encapsulation efficiency (Y2-%) and size (Y3-nm). Out of six investigated factors, four of them were identified as critical parameters affecting the studied responses. PLP molar concentration and the molar ratio of DPPC to MPEG-2000-DSPE had a positive impact on both Y1 and Y2, while the rotation speed at the formation of the lipid film had a negative impact. Y3 was highly influenced by prednisolone molar concentration and extrusion temperature. The accuracy and robustness of the model was further on confirmed. The developed model was used to optimize the formulation of LCL-PLP for efficient accumulation of the drug to tumor tissue. The cytotoxicity of the optimized LCL-PLP on C26 murine colon carcinoma cells was assessed. LCL-PLP exerted significant anti-angiogenic and anti-inflammatory effects on M2 macrophages, affecting indirectly the C26 colon carcinoma cell proliferation and development. 相似文献
59.
60.
Ahrens B 《New biotechnology》2011,28(5):530-537
In the past century, incidences of chronic metabolic diseases, such as obesity and type II diabetes, have increased dramatically. Obesity and abnormal insulin level are associated with a wide variety of health problems including a markedly increased risk for type II diabetes, fatty liver, hepato-biliary and gallbladder diseases, cardiovascular pathologies, neurodegenerative disorders, asthma and a variety of cancers. The development of therapeutic antibodies has evolved over the past decades into a mainstay of therapeutic options for patients with inflammatory diseases and cancer, while other indication areas such as metabolic diseases have so far only been rarely addressed. Although therapeutic antibodies might have advantages over current type II diabetes treatments like favorable serum half-life and high specificity, their development is also likely to face obstacles. For example the technical feasibility of antibody generation against G protein coupled receptors and transporters is challenging, patient compliance for a likely needle application might be limited, bioavailability in organs involved in the pathogenesis like the brain might be suboptimal and reimbursement issues for high treatment costs have to be taken into account. The current review focuses on the pathogenesis and standard therapeutic approaches as well as antibodies in development and potential antibody targets for type II diabetes. 相似文献