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931.
Paul Kruszka Tommy Hu Sungkook Hong Rebecca Signer Benjamin Cogné Betrand Isidor Sarah E. Mazzola Jacques C. Giltay Koen L. I. van Gassen Eleina M. England Lynn Pais Charlotte W. Ockeloen Pedro A. Sanchez‐Lara Esther Kinning Darius J. Adams Kayla Treat Wilfredo Torres‐Martinez Maria F. Bedeschi Maria Iascone Stephanie Blaney Oliver Bell Tiong Y. Tan Marie‐Ange Delrue Julie Jurgens Brenda J. Barry Elizabeth C. Engle Sarah K. Savage Nicole Fleischer Julian A. Martinez‐Agosto Kym Boycott Elaine H. Zackai Maximilian Muenke 《American journal of medical genetics. Part A》2019,179(10):2075-2082
Zinc finger protein 462 (ZNF462) is a relatively newly discovered vertebrate specific protein with known critical roles in embryonic development in animal models. Two case reports and a case series study have described the phenotype of 10 individuals with ZNF462 loss of function variants. Herein, we present 14 new individuals with loss of function variants to the previous studies to delineate the syndrome of loss of function in ZNF462. Collectively, these 24 individuals present with recurring phenotypes that define a multiple congenital anomaly syndrome. Most have some form of developmental delay (79%) and a minority has autism spectrum disorder (33%). Characteristic facial features include ptosis (83%), down slanting palpebral fissures (58%), exaggerated Cupid's bow/wide philtrum (54%), and arched eyebrows (50%). Metopic ridging or craniosynostosis was found in a third of study participants and feeding problems in half. Other phenotype characteristics include dysgenesis of the corpus callosum in 25% of individuals, hypotonia in half, and structural heart defects in 21%. Using facial analysis technology, a computer algorithm applying deep learning was able to accurately differentiate individuals with ZNF462 loss of function variants from individuals with Noonan syndrome and healthy controls. In summary, we describe a multiple congenital anomaly syndrome associated with haploinsufficiency of ZNF462 that has distinct clinical characteristics and facial features. 相似文献
932.
933.
H F Dullens R van Walraven M Klomberg L P Rademakers I C de Goey W den Otter 《Immunobiology》1988,177(3):293-304
Immunization of C57BL mice with one inoculum of 10(7) DBA/2-derived SL2 lymphosarcoma cells resulted in a +/- 20-fold increase in the total number of peritoneal cells. The number of macrophages showed a 10-fold increase from 3 x 10(6) (control mice) to 3.4 x 10(7) cells at day 8 after immunization. Within this macrophage population, four different cell types, based on the ultrastructural peroxidatic activity patterns, could be distinguished: exudate macrophages, resident macrophages, resident-exudate macrophages and peroxidatic-activity-negative macrophages. The number of exudate macrophages significantly increased in the peritoneal cavity after immunization: at day 8 after immunization, a peak value of 10(7) cells was observed. At the same time, there were 2.2 x 10(7) peroxidase-activity-negative macrophages present (representing the control value x 50). Significant in vitro tumoricidal activity of the isolated macrophages could not be measured until 8 days after immunization. At that time, a cytotoxicity index of 68 was reached. After immunization of the C57BL mice with 3 injections with allogeneic SL2 cells, there were no dramatic changes in the number of peritoneal cells after the last immunization. Only immediately after the last immunization was a minor increase in peroxidatic-activity-negative macrophages seen. But already at 5 days after the last immunization, the composition of the peritoneal suspension was similar to that of non-immunized mice with predominantly resident macrophages. The cytotoxicity of the peritoneal macrophages from hyperimmunized mice was constantly high during 1-15 days after the last immunization (cytotoxicity index ranged from 66-72). In order to study which type(s) of macrophage(s) (resident, exudate, resident-exudate or peroxidatic-activity-negative) is/are responsible for the cytotoxicity measured in vitro, peritoneal cell suspensions (obtained after immunization) were fractionated according to their affinity to wheat germ agglutinin (WGA) coupled to Sepharose columns. Comparison of the values of cytotoxicity measured before and after separation into "subtypes" of the macrophages revealed that the expression of cytotoxicity is not correlated with any of the "sub-types", especially when the peroxidatic activity pattern is is taken as a criterion. 相似文献
934.
Monique Gromm Richard van der Valk Karen Sliedregt Leen Vernie Rob Liskamp Günter Hmmerling Jens-Oliver Koopmann Frank Momburg Jacques Neefjes 《European journal of immunology》1997,27(4):898-904
The major histocompatibility complex (MHC)-encoded transporter associated with antigen processing (TAP) translocates peptides from the cytosol into the lumen of the endoplasmic reticulum. This step precedes the binding of peptides to MHC class I molecules and is essential for cell surface expression of the MHC class I/peptide complex. TAP has a broad sequence specificity and a preference for peptides of around 9 amino acids. To synthesize inhibitors for TAP, we studied various alterations of the peptide substrate. The results indicate that TAP is stereospecific and that peptide bonds engineered into isosteric structures can improve translocation of the peptide. Furthermore, TAP is able to translocate peptides with large side chains that correspond to a peptide of ~ 21 amino acids in extended conformation. Peptides with longer side chains compete for the peptide binding site of TAP but fail to be translocated. Therefore, they represent the first rationally designed inhibitors of TAP. 相似文献
935.
Functional characterization of a sialyltransferase-deficient mutant of Neisseria gonorrhoeae. 下载免费PDF全文
M J Gill D P McQuillen J P van Putten L M Wetzler J Bramley H Crooke N J Parsons J A Cole H Smith 《Infection and immunity》1996,64(8):3374-3378
Previous studies indicate that sialylation of lipopolysaccharide (LPS) by host CMP-N-acetylneuraminic acid (CMP-NANA) catalyzed by bacterial sialyltransferase rendered gonococci resistant to killing by phagocytes, to entry into epithelial cell lines, to killing by immune serum and complement, and to absorption of complement component C3. These results have been confirmed by comparing a sialyltransferase-deficient mutant (strain JB1) with its parent (strain F62) in appropriate tests. In contrast to F62, JB1 was very susceptible to killing by human polymorphonuclear phagocytes in opsonophagocytosis tests and incubation with CMP-NANA did not decrease the level of killing. The inherent resistance of F62 in these tests was probably due to LPS sialylation by CMP-NANA and lactate present in the phagocytes. A JB1 variant expressing the invasion-associated Opa protein was as able to enter Chang human conjunctiva epithelial cells as an Opa-positive variant of F62, suggesting that the sialyltransferase is not required for Opa-mediated entry. After incubation with CMP-NANA, the number of F62 variant gonococci entering cells but not that of JB1 variant gonococci was drastically reduced. Both JB1 and F62 were killed by incubation with rabbit antibody to gonococcal major outer membrane protein, protein I, and human complement, but only F62 was rendered resistant to the killing by incubation with CMP-NANA. Finally, both JB1 and F62 absorbed similar amounts of complement component C3 and the binding was decreased by incubation with CMP-NANA only for the wild type, F62. 相似文献
936.
H. L. Journée A. C. van Bruggen J. J. van der Meer A. B. de Jonge J. J. A. Mooij 《Medical & biological engineering & computing》1995,33(2):140-144
The recording of sounds over the oribt of the eye has been found to be useful in the detection of intracranial aneurysms.
A hydrophone for auscultation over the eye has been developed and is tested under controlled conditions. The tests consist
of measurement over the eyes in three healthy volunteers at rest, during voluntary breathing, during eyeball movements and
during sustained orbicular muscular contractions. Furthermore, measurements are performed at the side of the nose. Major features
of the hydrophonic transducer are high sensitivity to physiological sounds and a high degree of insensitivity to environmental
sounds propagated through the air. It can be concluded that the hydrophone may be useful for the early detection of intracranial
aneurysms and also for apnoea detection. 相似文献
937.
Effects of Colloidal Resuscitation Fluids on Reticuloendothelial Function and Resistance to Infection after Hemorrhage 总被引:3,自引:0,他引:3 下载免费PDF全文
Ed A. M. van Rijen Jason J. Ward Roderick A. Little 《Clinical and Vaccine Immunology : CVI》1998,5(4):543-549
The effects of three resuscitation fluids, hydroxyethyl starch (HES), Haemaccel, and fresh autologous blood, on reticuloendothelial system phagocytic and catabolic functions and resistance to infection after 40% hemorrhages in BALB/c mice were studied. The mice, anesthetized with isoflurane, were bled over a 10-min period, left hypovolemic for 30 min, and then resuscitated with their shed blood or the same volume of asanguineous fluid. Normothermia was maintained throughout the experiments. The uptake and catabolism of intravenously injected double-labelled sheep erythrocytes (51Cr-125I-SRBC) in liver and spleen were determined at 1 and 48 h after hemorrhage. No significant changes in the uptake or catabolism of SRBC in liver or spleen were found at 1 h after hemorrhage and resuscitation with any of the fluids. However, at 48 h a significant increase in liver uptake of SRBC was seen in animals resuscitated with either Haemaccel or HES compared to that in animals resuscitated with shed blood or in animals subjected to a sham operation. The increase in liver uptake was accompanied by a small decrease in spleen uptake in animals resuscitated with Haemaccel but not with HES. No great changes in catabolic activity were seen at 48 h, although activity levels tended to be higher in animals resuscitated with Haemaccel. Separate groups of animals were challenged by an intraperitoneal injection with live Escherichia coli at 1 or 48 h after hemorrhage and resuscitation. Sixty-four percent of the animals resuscitated with shed blood survived the challenge with E. coli at 1 h after hemorrhage, whereas only 10 and 0% survival was seen for animals resuscitated with Haemaccel and HES, respectively. At 48 h survival was 80% for shed-blood-resuscitated animals and 60 and 70% for Haemaccel- and HES-resuscitated animals, respectively. 相似文献
938.
Characterization of monocyte maturation in adherent and suspension cultures and its application to study monocyte differentiation in Hodgkin's disease. 下载免费PDF全文
P H de Mulder H van Rennes P D Mier M Bergers B E de Pauw C Haanen 《Clinical and experimental immunology》1983,54(3):681-688
Monocytes purified with cell scatter monitored counterflow centrifugation were cultured in plastic (adherent) and in teflon culture bags (suspension). Sequential changes were monitored during 15 days by measuring intracellular activity of three enzymes of intermediary metabolism: glucose-6-phosphate dehydrogenase (G-6-PDH), phosphohexose isomerase (PHI) and isocitrate dehydrogenase (ICDH), and the two acid hydrolases: acid phosphatase (ACP) and N-acetyl-beta-glucosaminidase (NAG). In teflon grown macrophages a significantly lower G-6-PDH activity was seen after 15 days in comparison to plastic adherent macrophages (P less than 0.0002). For the other enzymes similar values for both culture modalities were found. The significantly, cycloheximide insensitive, higher values for G-6-PDH, PHI and ICDH in 2 h plastic adherent monocytes in comparison with plastic non-adherent monocytes, suggest a relationship between adherent capacity and the level of intermediary metabolism. The overall yield of plastic adherent macrophages after 15 days was 35% in contrast with 89% for the in suspension cultured macrophages. This corroborates the existence of adherent and non-adherent monocytes, both capable of differentiation in vitro. In 14 patients with advanced Hodgkin's disease (HD) and 14 normal controls, monocyte differentiation was studied applying both culture modalities. The enzyme levels, reflecting growth and intermediary metabolism, were similar for both groups. The adherent capacity and yield, both in teflon and in plastic, after 15 days was comparable for both groups. It was concluded that in vitro monocyte differentiation in the presence of autologous serum was qualitatively and quantitatively normal in advanced HD; this is in favour of an intrinsically normal function of monocytes in HD. 相似文献
939.
Asero R Mistrello G Roncarolo D de Vries SC Gautier MF Ciurana CL Verbeek E Mohammadi T Knul-Brettlova V Akkerdaas JH Bulder I Aalberse RC van Ree R 《International archives of allergy and immunology》2000,122(1):20-32
BACKGROUND: Lipid transfer proteins (LTPs) are small molecules of approximately 10 kD that demonstrate high stability. They have recently been identified as allergens in the Rosaceae subfamilies of the Prunoideae (peach, apricot, plum) and of the Pomoideae (apple). They belong to a family of structurally highly conserved proteins that are also present in non-Rosaceae vegetable foods. OBJECTIVE: The aim of this study was to investigate the cross-reactivity to non-Rosaceae LTPs, and to study the role of protein stability in allergenicity. METHODS: Thirty-eight patients with a positive SPT to Rosaceae fruit extracts enriched for LTP were characterized by interview and SPT. To investigate IgE cross-reactivity between Rosaceae and non-Rosaceae LTPs, RAST and RAST inhibition as well as ELISA and ELISA inhibition were performed, using whole food extracts and purified LTPs. Both purified natural LTPs (peach, carrot and broccoli) and Pichia pastoris recombinant LTPs (carrot and wheat) were included. Pepsin digestion was used to address the role of stability in the allergenicity of LTPs. RESULTS: IgE antibodies to Rosaceae LTPs reacted to a broad range of vegetable foods, including Gramineae (cereals), Leguminosae (peanut), Juglandaceae (walnut), Anacardiaceae (pistachio), Brassicaceae (broccoli), Umbelliferae (carrot, celery), Solanaceae (tomato), Cucurbitaceae (melon), and Actinidiaceae (kiwi). Binding and inhibition studies with purified natural and recombinant LTPs confirmed their role in this cross-reactivity. Many of these cross-reactivities were accompanied by clinical food allergy, frequently including systemic reactions. Antibody binding to LTP was shown to be resistant to pepsin treatment of whole extract or purified LTP. CONCLUSION: LTP is a pan-allergen with a degree of cross-reactivity comparable to profilin. Due to its extreme resistance to pepsin digestion, LTP is a potentially severe food allergen. 相似文献
940.
Shadlen MF Larson EB Wang L Phelan EA McCormick WC Jolley L Teri L van Belle G 《Neurobiology of aging》2005,26(1):17-24
OBJECTIVES: To assess the influence of education on the association between apolipoprotein E and cognitive change. DESIGN: Prospective cohort. PARTICIPANTS: HMO-based sample of 2168 non-demented community-dwelling elderly followed over 6 years. MEASUREMENTS: Generalized estimating equations were used with the difference between baseline and follow-up cognitive abilities screening instrument (CASI) as the outcome variable. RESULTS: At follow-up, 6% of the sample had a decline of 1.5 S.D. or greater on the CASI. Compared to individuals without an APOE4 allele, individuals with a single APOE4 allele did not have greater CASI decline. By contrast, individuals with two APOE4 alleles experienced greater decline in cognitive performance and the magnitude of that decline decreased as years of educational attainment increased. These relationships held after adjusting for age, gender, ethnicity, depression, diabetes, and history of vascular disease. CONCLUSION: Lower education was associated with steep 4-year cognitive decline for APOE4 homozygotes but not for APOE4 heterozygotes. Potentially modifiable host factors such as education could influence the association of high-risk genotypes and cognitive decline. 相似文献