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81.
Sjoberg M Salazar T Espinosa C Dagnino A Avila A Eggers M Cassorla F Carvallo P Mericq MV 《The Journal of clinical endocrinology and metabolism》2001,86(9):4375-4381
We hypothesized that some children with idiopathic short stature in Chile might bear heterozygous mutations of the GH receptor. We selected 26 patients (3 females, 23 males) from 112 patients who consulted for idiopathic short stature at the University of Chile. Their chronological age was 8.3 +/- 1.9, and bone age was 6.1 +/- 1.0 yr. Their height was -3.0 +/- 0.7 SDS; IGF-I, -1.2 +/- 1.1 SD; IGF binding protein 3, -0.7 +/- 2.0 SDS; and GH binding protein, 0.4 +/- 0.8 SDS. Patients were admitted, and blood samples were obtained every 20 min to determine GH concentrations overnight. Coding sequences and intron-exon boundaries of exons 2-10 of GH receptor gene were amplified by PCR and subsequently analyzed through single-strand conformational analysis. Mean serum GH concentration, over 12-h, was 0.20 +/- 0.08 nM; pulse amplitude, 0.40 +/- 0.15 nM; number of peaks, 5.8 +/-1.5 peaks/12 h; peak value of GH during the 12-h sampling, 1.03 +/- 0.53 nM; and area under the curve, 151.4 +/- 56.1 nM/12 h. There were positive correlations between mean GH vs. area under the curve (P < 0.001) and GH peak (P < 0.01). The single-strand conformational analysis of the GH receptor gene showed abnormal migration for exon 6 in 9 patients and for exon 10 in 9 patients, which (by sequence analysis) corresponded to 2 polymorphisms of the GH receptor gene: an A-to-G transition in third position of codon 168 in exon 6 and a C-to-A transversion in the first position of codon 526 in exon 10. We further sequenced all coding exons and intron-exon boundaries in the most affected patients (nos. 6, 9, 11, 14, 15, 16, and 23). This analysis revealed a C-to-T transition in codon 161 of exon 6 in patient 23, which results in an amino acid change (Arg to Cys) in an heterozygous form in the patient and his father. In conclusion, the results of our study suggest that, in Chilean patients with idiopathic short stature, GH receptor gene mutations are uncommon, although we cannot exclude mutations that were missed by single-strand conformational analysis or mutations within introns or in the promoter regions of the GH receptor gene. 相似文献
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Pedro David Delgado López Beatriz Blanco de Val José Luis López Martínez Elena Araus Galdós Antonio Rodríguez Salazar 《Neurocirugía (Asturias, Spain)》2021,32(2):99-104
It is an increasingly common practice to indicate a carotid endarterectomy procedure based on the information provided by non-invasive tests like Duplex ultrasound, MR angiography or CT angiography, thereby obviating the performance of a conventional cerebral angiography. We present a case of symptomatic left carotid artery 80% stenosis in which cerebral angiography showed absence of the right A1 segment and bilateral anterior cerebral artery territories that filled only from a left injection. Just 90 seconds after carotid artery clamping at the neck, brain oximetry and somatosensory evoked potentials significantly dropped, that recovered after immediate clamp removal. Endarterectomy was dismissed and a carotid stent was successfully placed. This case highlights the importance of knowing the dynamics of cerebral blood circulation distal to the stenosis. If endarterectomy had been attempted, unawareness of the information provided by the cerebral angiography would have likely result in severe bi-hemispheric ischemia. 相似文献
84.
Eric Salazar Paul A. Christensen Edward A. Graviss Duc T. Nguyen Brian Castillo Jian Chen Bevin V. Lopez Todd N. Eagar Xin Yi Picheng Zhao John Rogers Ahmed Shehabeldin David Joseph Faisal Masud Christopher Leveque Randall J. Olsen David W. Bernard Jimmy Gollihar James M. Musser 《The American journal of pathology》2021,191(1):90-107
85.
Joana I. Meier Patricio A. Salazar Marek Ku
ka Robert William Davies Andreea Drau Ismael Alds Olivia Box Power Nicola J. Nadeau Jon R. Bridle Campbell Rolian Nicholas H. Barton W. Owen McMillan Chris D. Jiggins Yingguang Frank Chan 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(25)
Genetic variation segregates as linked sets of variants or haplotypes. Haplotypes and linkage are central to genetics and underpin virtually all genetic and selection analysis. Yet, genomic data often omit haplotype information due to constraints in sequencing technologies. Here, we present “haplotagging,” a simple, low-cost linked-read sequencing technique that allows sequencing of hundreds of individuals while retaining linkage information. We apply haplotagging to construct megabase-size haplotypes for over 600 individual butterflies (Heliconius erato and H. melpomene), which form overlapping hybrid zones across an elevational gradient in Ecuador. Haplotagging identifies loci controlling distinctive high- and lowland wing color patterns. Divergent haplotypes are found at the same major loci in both species, while chromosome rearrangements show no parallelism. Remarkably, in both species, the geographic clines for the major wing-pattern loci are displaced by 18 km, leading to the rise of a novel hybrid morph in the center of the hybrid zone. We propose that shared warning signaling (Müllerian mimicry) may couple the cline shifts seen in both species and facilitate the parallel coemergence of a novel hybrid morph in both comimetic species. Our results show the power of efficient haplotyping methods when combined with large-scale sequencing data from natural populations.Understanding how changes in DNA sequence affect traits and shape the evolution of populations and species has been a defining goal in genetics and evolution (1–3). DNA is naturally organized in the genome as long molecules consisting of linked chromosome segments. Linkage is a core concept in genetics: in genetic mapping, geneticists map causal variants not by tracking the actual mutation but through many otherwise neutral and unremarkable linked variants. Likewise, the detection of selection relies on observing hitchhiking of linked variants rather than seeing the mutation itself. This recognition makes it all the more paradoxical that haplotype information is routinely omitted from most genomic studies as a technical compromise. Lacking haplotype information not only complicates analysis and ancestry reconstruction but also precludes detection of allele-specific expression (4) and chromosome rearrangements and reduces power to detect selective sweeps, even entirely missing them when multiple haplotypes sweep together (5). Instead of sequencing genomes as haplotypes, short-read sequencing produces 150-bp reads. Until long-read platforms become sufficiently accurate and affordable, this lack of haplotype context will continue to impact mapping and genomic studies, particularly those in nonmodel organisms.One way to simplify haplotype reconstruction and inference from sequencing data is to avoid discarding haplotype information in the first place. A promising emerging technique is linked-read (LR) sequencing (6–9), which preserves long-range information via molecular barcoding of long DNA molecules before sequencing. Individual short reads can then be linked via a shared barcode to reconstruct the original haplotype. However, existing options all suffer from high cost, poor scalability, and/or require custom sequencing primers or settings that have thus far prevented them from being applied as the default sequencing platform (SI Appendix, Tables S1 and S2). If LR sequencing could become scalable and affordable, it would significantly advance genetics by enabling the “haplotyping” of entire populations (i.e., the sequencing and systematic discovery of genomic variants as haplotypes in hundreds or even thousands of samples in model and nonmodel organisms alike).Here, we describe a solution called “haplotagging,” a simple and rapid protocol for LR sequencing. Importantly, haplotagging maintains full compatibility with standard Illumina sequencing and can easily scale to large populations with no extra costs. We demonstrate this in three steps. First, we show that direct haplotyping using haplotagging is robust in single human and mouse samples with known haplotypes (“phases”). Next, we show the feasibility of population haplotyping in 245 mice, even with very low-coverage LR sequencing. Finally, we apply haplotagging to investigate the emergence of a hybrid morph in a hybrid zone system in Ecuador featuring 670 individuals of two species of Heliconius butterflies. 相似文献
86.
OBJECTIVE: We have previously observed low levels of high density lipoprotein (HDL) cholesterol in active sarcoidosis. The aim of this study was to analyze the role of serum amyloid A (SAA) on this lipid disorder. METHODS: Eighty five untreated sarcoid patients, 40 with active disease and 45 with inactive disease, were recruited. Sarcoidosis activity was evaluated by means of clinical, chest X-ray, gallium-67 scan, serum angiotensin converting enzyme (peptidyl-dipeptidase A) values, and pulmonary function tests. Analysis of lipoprotein metabolism included: serum cholesterol, low density lipoprotein (LDL)-cholesterol, HDL-cholesterol, HDL(2)-cholesterol, HDL(3)-cholesterol, apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), and triglyceride concentrations. Serum amyloid A protein and lecithin-cholesterol acyltransferase (LCAT) activity were measured. RESULTS: In active sarcoidosis we found significantly reduced levels of HDL-cholesterol (1.17+/-0.36 vs. 1. 44+/-0.39 mmol/l, P=0.002), HDL(3)-cholesterol (0.78+/-0.23 vs. 1. 02+/-0.21 mmol/l, P<0.0001), and apo A-I (1.36+/-0.29 vs. 1.61+/-0. 27 g/l, P<0.0001) and significantly increased levels of triglyceride (1.51+/-0.64 vs. 1.03+/-0.46 mmol/l, P<0.0001), and apo B (1.14+/-0. 25 vs. 0.99+/-0.27 g/l, P=0.012) versus inactive sarcoidosis. Serum amyloid A concentrations were significantly increased in the patients with active disease (155.45+/-154.01 mg/ml) compared to the inactive sarcoid patients (89.70+/-65.36 mg/ml) (P=0.011). There were no significant differences in cholesterol, LDL-cholesterol, HDL(2)-cholesterol or LCAT values between groups. Multivariate logistic regression analysis showed that HDL-cholesterol (regression coefficient b=-1.96; S.E.=0.87; P=0.02) and SAA (regression coefficient b=0.01; S.E.=0.004; P=0.01) were the two variables independently associated with disease activity. Moreover, a significant negative correlation was observed between SAA levels and both HDL-cholesterol (r=-0.39; P=0.01) and apo A-I (r=-0.35; P=0.03) levels, in the active sarcoid group. Conversely, no correlation was found in the inactive sarcoid group. CONCLUSION: The low HDL-cholesterol and apo A-I concentrations seen in active sarcoid patients are associated with a significant increase of SAA levels. We suggest that the displacement of apo A-I by SAA on HDL accounts for the lower level of HDL-cholesterol seen in active sarcoidosis. 相似文献
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Sara García‐Jiménez German Bernal Fernández Maria Fernanda Martínez Salazar Antonio Monroy Noyola Cairo Toledano Jaimes Angelica Meneses Acosta Leticia Gonzalez Maya Elizabeth Aveleyra Ojeda Maria A. Terrazas Meraz Boll Marie‐Catherine Miguel A. Sánchez‐Alemán 《Journal of clinical laboratory analysis》2015,29(1):5-9
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90.
Our purpose is to correlate thin section CT of peripheral bronchogenic carcinomas with histologically detected lymphatic or vascular invasion. Retrospective 3-year database search revealed 186 surgical resections for primary bronchogenic carcinoma, of which 58 had available preoperative imaging performed at our institution. Cases with prior surgery, nonconfirmatory pathology, remote imaging, or central location were excluded, resulting in a study population of 42 patients, 25 men, 17 women, with a mean age of 69 years. Imaging with 1-3 mm collimation was performed within a mean of 32 days prior to surgery. Histologic diagnoses included adenocarcinoma (n = 24, 57%), squamous cell carcinoma (n = 13, 31%), large cell carcinoma (n = 4, 10%), and small cell carcinoma (n = 1, 2%), with a mean tumor size of 27 mm. Three radiologists blindly and independently recorded bronchovascular thickening, septal and nonseptal opacities, and the extent of each beyond tumor margins: 1) <5 mm, 2) 5-10 mm, and 3) >10 mm. Lymphangio-invasion was correlated with imaging findings, tumor size, and histology. Adjacent parenchymal abnormalities were recorded in 40 (95%) of 42 masses, with isolated nonseptal opacities representing the most frequent abnormality in 21 (50%), followed by bronchovascular thickening in 16 (38%), and septal opacities in 12 (29%). Lymphangio-invasion was present in 16 (38%) of cases. The frequency of lymphangio-invasion was highest (53%) in cases with 2 or more positive findings, and extension beyond 10mm from the tumor margin. This trend did not achieve statistical significance by ROC analysis. Lymphangio-invasion was positively correlated with tumor size, P =.03, but not histology.In conclusion, parenchymal abnormalities beyond tumor margins shown by CT may be due to lymphangio-invasion but imaging findings did not reliably distinguish cases with and without lymphangio-invasion. 相似文献