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91.
92.
Investigation of a Family with Autosomal Dominant Dilated Cardiomyopathy Defines a Novel Locus on Chromosome 2q14-q22 总被引:4,自引:0,他引:4 下载免费PDF全文
Martin Jung Imke Poepping Andreas Perrot Annette E. Ellmer Thomas F. Wienker Rainer Dietz André Reis Karl Josef Osterziel 《American journal of human genetics》1999,65(4):1068-1077
Dilated cardiomyopathy (DCM) is a leading cause of heart failure and the most frequent indication for heart transplantation in young patients. Probably >25% of DCM cases are of familial etiology. We report here genetic localization in a three-generation German family with 12 affected individuals with autosomal dominant familial DCM characterized by ventricular dilatation, impaired systolic function, and conduction disease. After exclusion of known DCM loci, we performed a whole-genome screen and detected linkage of DCM to chromosome 2q14-q22. Investigation of only affected individuals defines a 24-cM interval between markers D2S2224 and D2S2324; when unaffected individuals are also included, the critical region decreases to 11 cM between markers D2S2224 and D2S112, with a peak LOD score of 3.73 at recombination fraction 0 at D2S2339. The identification of an additional locus for familial autosomal dominant DCM underlines the genetic heterogeneity and may assist in the elucidation of the causes of this disease. 相似文献
93.
Ran Liu Miao Yang Yanli Meng Juan Liao Jingyi Sheng Yuepu Pu Lihong Yin Sun Jung Kim 《PloS one》2013,8(10)
Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3′UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC. 相似文献
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95.
Ji Young Hwang Kyung Min Lee Yun Hwa Kim Hye Min Shim Young Kyung Bae Jung Hye Hwang Hosun Park 《Experimental Animals》2014,63(1):63-72
Coxsackieviruses are important pathogens in children and the outcomes of neonatal
infection can be serious or fatal. However, the outcomes of coxsackievirus infection
during early gestation are not well defined. In this study, we examined the possibility of
vertical transmission of coxsackievirus B3 (CVB3) and the effects of CVB3 infection on
early pregnancy of ICR mice. We found that the coxsackievirus and adenovirus receptor
(CAR) was highly expressed not only in embryos but also in the uterus of ICR mice. CVB3
replicated in the uterus 1 to 7 days post-infection (dpi), with the highest titer at 3
dpi. The pregnancy loss rate in mice infected with CVB3 during early gestation was 38.3%,
compared to 4.7% and 2.7% in mock-infected and UV-inactivated-CVB3 infected pregnant mice,
respectively. These data suggest that the uterus and embryo, which express abundant CAR,
are important targets of CVB3 and that the vertical transmission of CVB3 during early
gestation induces pregnancy loss. 相似文献
96.
Caspase-11 is an inducible caspase involved in the regulation of cell death and inflammation. In the present study, we examined whether apoptosis signal-regulating kinase 1 (Ask1)-mediated signaling pathway is involved in the expression of caspase-11 induced by lipopolysaccharide (LPS). We found that the induction of caspase-11 was suppressed by the inhibitors of NADPH oxidase (Nox) or knockdown of Nox4 that acts downstream of toll-like receptor 4 and generates Ask1-activating reactive oxygen species. Overexpression of dominant negative tumor necrosis factor receptor associate factor 6 also suppressed the induction of caspase-11. Importantly, knockdown or dominant negative form of Ask1 suppressed the induction of caspase-11 following LPS stimulation. Taken together, our results show that Ask1 regulates the expression of caspase-11 following LPS stimulation. 相似文献
97.
Plants,microorganisms, and soil temperatures contribute to a decrease in methane fluxes on a drained Arctic floodplain 下载免费PDF全文
Min Jung Kwon Felix Beulig Iulia Ilie Marcus Wildner Kirsten Küsel Lutz Merbold Miguel D. Mahecha Nikita Zimov Sergey A. Zimov Martin Heimann Edward A. G. Schuur Joel E. Kostka Olaf Kolle Ines Hilke Mathias Göckede 《Global Change Biology》2017,23(6):2396-2412
As surface temperatures are expected to rise in the future, ice‐rich permafrost may thaw, altering soil topography and hydrology and creating a mosaic of wet and dry soil surfaces in the Arctic. Arctic wetlands are large sources of CH4, and investigating effects of soil hydrology on CH4 fluxes is of great importance for predicting ecosystem feedback in response to climate change. In this study, we investigate how a decade‐long drying manipulation on an Arctic floodplain influences CH4‐associated microorganisms, soil thermal regimes, and plant communities. Moreover, we examine how these drainage‐induced changes may then modify CH4 fluxes in the growing and nongrowing seasons. This study shows that drainage substantially lowered the abundance of methanogens along with methanotrophic bacteria, which may have reduced CH4 cycling. Soil temperatures of the drained areas were lower in deep, anoxic soil layers (below 30 cm), but higher in oxic topsoil layers (0–15 cm) compared to the control wet areas. This pattern of soil temperatures may have reduced the rates of methanogenesis while elevating those of CH4 oxidation, thereby decreasing net CH4 fluxes. The abundance of Eriophorum angustifolium, an aerenchymatous plant species, diminished significantly in the drained areas. Due to this decrease, a higher fraction of CH4 was alternatively emitted to the atmosphere by diffusion, possibly increasing the potential for CH4 oxidation and leading to a decrease in net CH4 fluxes compared to a control site. Drainage lowered CH4 fluxes by a factor of 20 during the growing season, with postdrainage changes in microbial communities, soil temperatures, and plant communities also contributing to this reduction. In contrast, we observed CH4 emissions increased by 10% in the drained areas during the nongrowing season, although this difference was insignificant given the small magnitudes of fluxes. This study showed that long‐term drainage considerably reduced CH4 fluxes through modified ecosystem properties. 相似文献
98.
The difference between the heat (T(G)) and the cold (T(G)') denaturation temperatures defines the temperature range (T(Range)) over which the native state of a reversible two-state protein is thermodynamically stable. We have performed a correlation analysis for thermodynamic parameters in a selected data set of structurally nonhomologous single-domain reversible two-state proteins. We find that the temperature range is negatively correlated with the protein size and with the heat capacity change (DeltaC(p)) but is positively correlated with the maximal protein stability [DeltaG(T(S))]. The correlation between the temperature range and maximal protein stability becomes highly significant upon normalization of the maximal protein stability with protein size. The melting temperature (T(G)) also shows a negative correlation with protein size. Consistently, T(G) and T(G)' show opposite correlations with DeltaC(p), indicating a dependence of the T(Range) on the curvature of the protein stability curve. Substitution of proteins in our data set with their homologues and arbitrary addition or removal of a protein in the data set do not affect the outcome of our analysis. Simulations of the thermodynamic data further indicate that T(Range) is more sensitive to variations in curvature than to the slope of the protein stability curve. The hydrophobic effect in single domains is the principal reason for these observations. Our results imply that larger proteins may be stable over narrower temperature ranges and that smaller proteins may have higher melting temperatures, suggesting why protein structures often differentiate into multiple substructures with different hydrophobic cores. Our results have interesting implications for protein thermostability. 相似文献
99.
The MHC class I-like IgG receptor controls perinatal IgG transport,IgG homeostasis,and fate of IgG-Fc-coupled drugs 总被引:1,自引:0,他引:1
Roopenian DC Christianson GJ Sproule TJ Brown AC Akilesh S Jung N Petkova S Avanessian L Choi EY Shaffer DJ Eden PA Anderson CL 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(7):3528-3533
Abs of the IgG isotype are efficiently transported from mother to neonate and have an extended serum t(1/2) compared with Abs of other isotypes. Circumstantial evidence suggests that the MHC class I-related protein, the neonatal FcR (FcRn), is the FcR responsible for both in vivo functions. To understand the phenotypes imposed by FcRn, we produced and analyzed mice with a defective FcRn gene. The results provide direct evidence that perinatal IgG transport and protection of IgG from catabolism are mediated by FcRn, and that the latter function is key to IgG homeostasis, essential for generating a potent IgG response to foreign Ags, and the basis of enhanced efficacy of Fc-IgG-based therapeutics. FcRn is therefore a promising therapeutic target for enhancing protective humoral immunity, treating autoimmune disease, and improving drug efficacy. 相似文献
100.