全文获取类型
收费全文 | 16919篇 |
免费 | 1093篇 |
国内免费 | 130篇 |
专业分类
耳鼻咽喉 | 144篇 |
儿科学 | 521篇 |
妇产科学 | 463篇 |
基础医学 | 2586篇 |
口腔科学 | 286篇 |
临床医学 | 1360篇 |
内科学 | 3952篇 |
皮肤病学 | 430篇 |
神经病学 | 2365篇 |
特种医学 | 455篇 |
外科学 | 1556篇 |
综合类 | 32篇 |
一般理论 | 1篇 |
预防医学 | 958篇 |
眼科学 | 185篇 |
药学 | 1215篇 |
中国医学 | 34篇 |
肿瘤学 | 1599篇 |
出版年
2024年 | 29篇 |
2023年 | 210篇 |
2022年 | 453篇 |
2021年 | 754篇 |
2020年 | 406篇 |
2019年 | 509篇 |
2018年 | 663篇 |
2017年 | 482篇 |
2016年 | 558篇 |
2015年 | 615篇 |
2014年 | 757篇 |
2013年 | 999篇 |
2012年 | 1425篇 |
2011年 | 1420篇 |
2010年 | 806篇 |
2009年 | 731篇 |
2008年 | 1195篇 |
2007年 | 1097篇 |
2006年 | 998篇 |
2005年 | 892篇 |
2004年 | 815篇 |
2003年 | 725篇 |
2002年 | 565篇 |
2001年 | 94篇 |
2000年 | 83篇 |
1999年 | 96篇 |
1998年 | 125篇 |
1997年 | 79篇 |
1996年 | 60篇 |
1995年 | 47篇 |
1994年 | 49篇 |
1993年 | 29篇 |
1992年 | 41篇 |
1991年 | 43篇 |
1990年 | 39篇 |
1989年 | 35篇 |
1988年 | 19篇 |
1987年 | 29篇 |
1986年 | 24篇 |
1985年 | 13篇 |
1984年 | 20篇 |
1983年 | 13篇 |
1982年 | 14篇 |
1981年 | 11篇 |
1980年 | 10篇 |
1979年 | 14篇 |
1978年 | 5篇 |
1975年 | 5篇 |
1974年 | 9篇 |
1970年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
Mancuso M Conforti FL Rocchi A Tessitore A Muglia M Tedeschi G Panza D Monsurrò M Sola P Mandrioli J Choub A DelCorona A Manca ML Mazzei R Sprovieri T Filosto M Salviati A Valentino P Bono F Caracciolo M Simone IL La Bella V Majorana G Siciliano G Murri L Quattrone A 《Neuroscience letters》2004,371(2-3):158-162
Mitochondrial impairment has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific polymorphisms were previously related to other neurodegenerative diseases, such as Parkinson, Friedreich and Alzheimer disease. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients with sALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individuals carrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the dataset by sex, age and site of onset of disease and survival failed to reach significance for association. Our study provides evidence of the contribution of mitochondrial variation to the risk of ALS development in Caucasians. Further it may help elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies for the treatment of this disease. 相似文献
72.
Francesca Grassi Aldo Giovannelli Sergio Fucile Elisabetta Mattei Fabrizio Eusebi 《Pflügers Archiv : European journal of physiology》1993,425(1-2):117-125
The cholinergic responses of the human tumour cell line TE671/RD were examined using digital Ca2+ imaging fluorescence microscopy and patch-clamp measurements. In response to stimulation of the muscarinic acetylcholine (ACh) receptor (mAChR), the intracellular concentration of Ca2+ ([Ca2+]i) rose about two-fold, in parallel with inositol 1,4,5-trisphosphate accumulation, measured by chromatographic techniques. By contrast, there was no increment of [Ca2+]i upon stimulation of the nicotinic ACh receptor (nAChR), nor after caffeine application. Electrophysiological experiments showed that TE671/RD cells lack functional voltage-activated Ca2+ channels. The stimulation of the nAChR induced transient whole-cell currents (I
ACh). Little or no current was detected in isotonic extracellular Ca2+, with Cs+ in the patch pipette. Cell pretreatment with muscarine reduced I
ACh by about 20%, without consistent modifications of current kinetics. Muscarine applied to the extra-patch membrane under the cell-attached configuration had no obvious effect on ACh-evoked unitary events. In conclusion, in human TE671/ RD cells, muscarinic stimulation increases [Ca2+]i, while nicotinic stimulation does not. In addition, the nAChR exhibits peculiar ion permeability properties and is not functionally regulated by the breakdown of phosphoinositides. 相似文献
73.
Mazzanti L Cicognani A Baldazzi L Bergamaschi R Scarano E Strocchi S Nicoletti A Mencarelli F Pittalis M Forabosco A Cacciari E 《American journal of medical genetics. Part A》2005,135(2):150-154
The identification of Y-chromosome material is important in females with Ullrich-Turner syndrome (UTS) due to the risk of developing gonadoblastoma or other gonadal tumors. There is controversy regarding the frequency of the Y-chromosome-derived material and the occurrence of gonadoblastoma in these patients. The aim of our study was to evaluate a large number of patients with UTS, followed before and during the pubertal age for the prevalence of Y-chromosome derived material, the occurrence of gonadoblastoma, and the incidence of possible neoplastic degeneration. An unselected series of 171 patients with UTS (1-34 years old), diagnosed cytogenetically, was studied for Y-chromosome markers (SRY and Y-centromeric DYZ3 repeats). The follow-up was of 2-22 years; 101 of these patients were followed during pubertal age. Y-chromosome material was found in 14 patients (8%): 12 of these were gonadectomized (2.8-25.9 years). A gonadoblastoma was detected in four patients under 16 years of age: in two, Y-material was detected only at molecular analysis (at conventional cytogenetic analysis, one was included in the 45,X group and one in the X + mar group) and one had also an immature teratoma and an endodermal sinus carcinoma. The prevalence of gonadoblastoma in our series of gonadectomized UTS patients with Y-positive material was of 33.3% (4/12). Our data suggest that the age of appearance and the possibility of malignant degeneration of gonadoblastoma can occur early in life. These patients, in particular those with 45,X or a marker chromosome may benefit from molecular screening to detect the presence of Y-chromosome material; PCR is a rapid and inexpensive technique. At the moment, laparoscopy and preventive gonadectomy performed as soon as possible remain the procedures of choice for patients with UTS, when Y-chromosome has been identified, as we are still unable to predict a future malignant evolution of gonadoblastoma. 相似文献
74.
Lasalvia A Bonetto C Malchiodi F Salvi G Parabiaghi A Tansella M Ruggeri M 《Psychological medicine》2005,35(11):1655-1665
BACKGROUND: Subjective quality of life has gained a crucial role as a global measure of outcome in mental health care. This study aimed to investigate the impact of meeting needs for care, as assessed by both patients and mental health professionals, to improve the subjective quality of life in a sample of patients receiving community-based psychiatric care. METHOD: The study was conducted using a 4-year prospective longitudinal design. A cohort of patients from the South-Verona Community-based Mental Health Service (CMHS) was assessed at baseline and follow-up using, among other social and clinical measures, the Camberwell Assessment of Need (both staff and patient versions) and the Lancashire Quality of Life Profile. Predictors of changes of subjective quality of life were explored using block-stratified multiple regression procedures. RESULTS: Improvement in patients' clinical conditions as well as the reduction in patient-rated unmet needs in the social domain predicted an increase in subjective quality of life over 4 years; changes in staff-rated needs did not show any association with changes in subjective quality of life. CONCLUSIONS: Meeting self-perceived social needs, beyond symptoms reduction, seems to be of particular importance for ensuring a better quality of life for people with mental disorders. If the main goal of mental health care is to improve the quality of life of users, a policy of actively addressing patient-rated needs should be implemented. 相似文献
75.
Acute dopamine/noradrenaline reuptake inhibition enhances human exercise performance in warm, but not temperate conditions 总被引:2,自引:2,他引:2
Phillip Watson Hiroshi Hasegawa Bart Roelands Maria Francesca Piacentini Roel Looverie Romain Meeusen 《The Journal of physiology》2005,565(3):873-883
Nine healthy endurance-trained males were recruited to examine the effect of a dual dopamine/noradrenaline reuptake inhibitor on performance, thermoregulation and the hormonal responses to exercise. Subjects performed four trials, ingesting either a placebo (pla) or 2 × 300 mg bupropion (bup), prior to exercise in temperate (18°C) or warm (30°C) conditions. Trials consisted of 60 min cycle exercise at 55% W max immediately followed by a time trial (TT). TT performance in the heat was significantly improved by bupropion (pla: 39.8 ± 3.9 min, bup: 36.4 ± 5.7 min; P = 0.046), but no difference between treatments was apparent in temperate conditions (pla: 30.6 ± 2.2 min, bup: 30.6 ± 1.9 min; P = 0.954). While TT power output was consistently lower in the heat when compared to temperate conditions, this decrement was attenuated by bupropion. At the end of the TT in the heat, both core temperature (pla 39.7 ± 0.3°C, bup 40.0 ± 0.3°C; P = 0.017) and HR (pla 178 ± 7 beats min−1 , bup 183 ± 12 beats min−1 ; P = 0.039), were higher in the bupropion trial than in the placebo. Circulating pituitary and adrenal hormone concentrations increased throughout exercise in all trials. Circulating serum prolactin was elevated above temperate levels during exercise in a warm environment ( P < 0.001). These data indicate that performance in warm conditions is enhanced by acute administration of a dual dopamine/noradrenaline reuptake inhibitor. No such effect was apparent under temperate conditions. It appears that bupropion enabled subjects to maintain a greater TT power output in the heat with the same perception of effort and thermal stress reported during the placebo trial, despite the attainment of a higher core temperature. 相似文献
76.
Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus 总被引:13,自引:0,他引:13
Asumalahti K Veal C Laitinen T Suomela S Allen M Elomaa O Moser M de Cid R Ripatti S Vorechovsky I Marcusson JA Nakagawa H Lazaro C Estivill X Capon F Novelli G Saarialho-Kere U Barker J Trembath R Kere J;Psoriasis Consortium 《Human molecular genetics》2002,11(5):589-597
PSORS1, near HLA-C, is the major genetic determinant of psoriasis. We present genetic and structural evidence suggesting a major role for the HCR gene at the PSORS1 locus. Genotyping of 419 families from six populations revealed that coding single-nucleotide polymorphisms of HCR formed a conserved allele HCR*WWCC that associated highly significantly with psoriasis and with the HLA-Cw6 allele in all populations. Because of strong linkage disequilibrium between HLA-Cw6 and HCR*WWCC, the two genes could not be genetically distinguished by this sample size. However, the variant HCR allele was predicted to differ in secondary structure from the wild-type protein. HCR protein expression in lesional psoriatic skin differed considerably from that observed in normal skin. These results provide strong evidence for the HCR*WWCC allele as a major genetic determinant for psoriasis, probably by a mechanism impacting on keratinocyte proliferation. 相似文献
77.
Reversible G(1) arrest by dimethyl sulfoxide as a new method to synchronize Chinese hamster cells 总被引:2,自引:0,他引:2
Dimethyl sulfoxide (DMSO), a well-known differentiation inducer in several myeloid cells, also induces a reversible G(1) arrest in many cell lines. We recently showed that DMSO induces a G(1) phase arrest in Chinese hamster ovary (CHO) cells, by restoring contact inhibition and preventing high density-dependent apoptosis. CHO cells are frequently used in cell biology and mutagenesis studies due to their good growth capacity and ease of manipulation but are very difficult to synchronize by serum starvation since they detach from monolayers when they reach confluence. In this study we investigated the possibility of using DMSO to reversibly synchronize CHO cells in the G(1) phase of the cell cycle and analysed whether toxic effects follow the arrest using growth curve, sister chromatid exchange and micronuclei assays. We carried out a kinetic analysis of the arrest by DMSO and re-entry into the cell cycle after drug release by cytofluorimetric analysis of DNA content and bromodeoxyuridine incorporation. We show that CHO cells are efficiently and reversibly arrested in G(1) by DMSO in concentrations ranging between 1 and 2%. In our experiments, >90% of cells grown for 96 h in presence of the drug were arrested in G(1) and synchronously re-entered S phase approximately 8-12 h after release. Furthermore, expression levels of p27 were down-regulated during G(1) progression and cyclin D3 and E expression patterns were similar to those observed after serum starvation. No detectable cytotoxicity or genetic damage were induced in G(1) released cells as revealed by the tests employed. Our results show that DMSO is a very powerful inducer of G(1) synchronization in CHO cells without detectable cytotoxic or genetic effects in cell populations released from G(1) arrest. DMSO synchronization represents a model system in which to analyse protein activities regulating G(1) progression and investigate the response of G(1) cells to mutagen treatments. 相似文献
78.
Calorini L Mannini A Bianchini F Mugnai G Balzi M Becciolini A Ruggieri S 《Clinical & experimental metastasis》1999,17(10):889-895
A previous study by our laboratory showed that the peritoneal murine Corynebacterium parvum-elicited macrophages released into their growth medium an activity which enhanced the ability of B16-F10 melanoma cells to
form experimental metastases in the lung of syngeneic mice. In the present study, we used a clone of B16-F10 line (F10-M3
cells) to investigate whether the increase in lung-colonizing potential due to the pro-clonogenic activity released by C. parvum-elicited macrophages was associated with biological properties characteristic of a metastatic phenotype. We have found that
the pulmonary retention, growth rate in lung parenchyma, invasiveness through Matrigel, adhesiveness to IL-1-activated endothelium
and MHC class I expression were increased in F10-M3 cells stimulated by the macrophage pro-clonogenic activity. By using an
in vitro experimental protocol, the enhancement of lung-colonizing potential in the stimulated melanoma cells turned out to be a transient
phenomenon as was the increase of invasiveness through Matrigel and the higher expression of MHC class I antigens. In conclusion,
the melanoma cells stimulated by the pro-clonogenic activity released by C. parvum-elicited macrophages showed changes in biological parameters which are relevant to metastatic diffusion. These changes appeared
as a temporary phenomenon which sustains the view that the metastatic phenotype represents a transient biological character
influenced by host factors.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
79.
Extraskeletal myxoid chondrosarcoma: multimodal diagnosis and identification of a new cytogenetic subgroup characterized by t(9;17)(q22;q11) 总被引:2,自引:0,他引:2
Bjerkehagen B Dietrich C Reed W Micci F Saeter G Berner A Nesland JM Heim S 《Virchows Archiv : an international journal of pathology》1999,435(5):524-530
Extraskeletal myxoid chondrosarcoma is a rare malignant soft tissue tumour that can be difficult to diagnose correctly, especially
preoperatively. We describe four cases of extraskeletal myxoid chondrosarcoma of the extremities diagnosed by a multimodal
approach. The cytological examination of fine-needle aspirates showed small and round, mildly pleomorphic cells lying in sheets
and cords, but also dispersed within a myxoid and metachromatic intercellular substance. Histological, electron microscopic
and immunocytochemical examination also yielded findings compatible with the diagnosis of extraskeletal myxoid chondrosarcoma.
Cytogenetic analysis demonstrated a t(9;22)(q22;q12) in two tumours and a t(9;17)(q22;q11) in the third and fourth. The translocation
t(9;22)(q22;q12) has been described repeatedly in extraskeletal myxoid chondrosarcoma but never in other tumours; hence, the
detection of this pathognomonic chromosome abnormality in short-term cultured cells from fine-needle aspirates verified the
diagnosis in two of the cases. The t(9;17)(q22;q11) found in the last two cases probably represents a new cytogenetic subgroup
of extraskeletal myxoid chondrosarcoma as it, too, is unknown in other contexts. The multimodal approach taken in these four
cases enabled a definite diagnosis of a rare malignant tumour whose cytological and histological features alone are usually
not sufficiently distinct to rule out other differential diagnostic possibilities.
Received: 16 March 1999 / Accepted: 1 June 1999 相似文献