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41.
Arterial endothelial function in a porcine model of early stage atherosclerotic vascular disease 总被引:2,自引:0,他引:2
Turk JR Henderson KK Vanvickle GD Watkins J Laughlin MH 《International journal of experimental pathology》2005,86(5):335-345
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States and is projected to become the leading cause of mortality in the world. Atherosclerosis is the most important single factor contributing to this disease burden. In this study, we characterize relationships between endothelial dysfunction and vascular disease in an animal model of diet-induced, early-stage atherosclerotic vascular disease. We tested the hypothesis that hypercholesterolaemia induces vascular disease and impairs endothelium-dependent relaxation (EDR) in conduit arteries of adult male Yucatan pigs. Pigs were fed a normal fat (NF) or high fat cholesterol (HFC) diet for 20-24 weeks. Results indicate that, while the HFC diet did not alter EDR in femoral or brachial arteries, EDR was significantly decreased in both carotid and coronary arteries. Sudanophilic fatty streaks were significantly present in the abdominal aorta and common carotid artery. Histopathology revealed increased intima-media thickness (IMT) and foam cell accumulation in Stary Stage I-III lesions in the abdominal aorta, common carotid artery and femoral arteries. In the coronary arteries, the accumulation of foam cells in Stary Stage I and II lesions resulted in a trend for increased IMT. There was no evidence of vascular disease in the brachial arteries. These results indicate that early stages of CVD (Stary Stage I-III) precede decreases in EDR induced by HFC diet, because femoral arteries exhibited foam cell accumulation and an increased IMT but no change in endothelial function. 相似文献
42.
43.
Mitogen-activated Xenopus laevis lymphocytes produce a T-cell growth factor. 总被引:1,自引:0,他引:1
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Mitogen-free and serum-free supernatants (SNs) from cultures of phytohaemagglutinin (PHA)-stimulated Xenopus splenocytes, co-stimulated thymocytes, induced proliferation of splenic and thymic lymphoblast and supported growth of alloreactive T-cell lines. These SNs had no effect on 'resting' splenocytes, as measured by uptake of tritiated thymidine ([3H]TdR). Growth-promoting activity was also detected in SNs of cultures containing alloreactive T-cell lines and either PHA or irradiated stimulator cells that expressed the original priming alloantigens. Thus, T lymphocytes appear to be involved in producing, as well as responding to, a Xenopus T-cell growth factor (TCGF). TCGF activity could be absorbed from these active SNs with PHA-activated splenic blasts. No functional cross-reactivity among different mammalian interleukin-2 (IL-2) and Xenopus TCGF preparations was detected. 相似文献
44.
A randomized controlled trial of an information booklet for hypertensive patients in general practice 总被引:1,自引:2,他引:1
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C.J. Watkins A.O. Papacosta S. Chinn J. Martin 《The British journal of general practice》1987,37(305):548-550
A randomized controlled trial of an information and medical record booklet designed to improve patient understanding and participation in the management of hypertension was conducted in six inner London general practices. After one year there were no significant differences between the group who had received the booklets and the control group in mean systolic or diastolic blood pressure, but the study group scored significantly higher on knowledge about hypertension and its management. However, the difference between the two groups was small, possibly because both groups started with a high level of understanding about hypertension and its management. In addition, the mean diastolic blood pressure in the control group showed that the treatment provided was already satisfactory, and that there was little need for improvement. Nevertheless, the information booklet evaluated in this study provides health professionals with a highly acceptable method of informing the patient about hypertension and its management and could be used both in hospital and general practice. 相似文献
45.
Unconventional therapies in asthma: an overview 总被引:2,自引:2,他引:2
Acupuncture, homoeopathy, mind-body therapies, and nutritional, herbal, and environmental medicine have all been used in the management of patients with asthma. This paper reviews the evidence base for the use of these unconventional or complementary therapics. Although there is a paucity of large randomized, controlled trials in this area, there is sufficient evidence to suggest that many of these therapies can produce objective and subjective benefit in selected groups of patients. In view of the increasing popularity of complementary medicine among patients and general practitioners, there is now an urgent need for high-quality research to determine how, or whether, these therapies may be interwoven with the more orthodox treatments currently available. 相似文献
46.
Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
47.
Heimberg Murray; Weinstein Ira; Klausner Howard; Watkins M. L. 《The American journal of physiology》1962,202(2):353-358
48.
49.
Varadharaj S Watkins T Cardounel AJ Garcia JG Zweier JL Kuppusamy P Natarajan V Parinandi NL 《Antioxidants & redox signaling》2005,7(1-2):287-300
Recent clinical trials have shown that vitamin C, at pharmacological concentrations (milligram to approximately gram), upon infusion into circulation, modulates vasodilation and vascular tone in humans. This also results in the elevated concentrations of vitamin C in circulation in the millimolar range. Here, it was hypothesized that vitamin C at pharmacological concentrations (millimolar) would induce oxidative stress and cause loss of redox-dependent cell viability in vascular endothelial cells (ECs). To test the hypothesis, bovine lung microvascular ECs (BLMVECs) in monolayer cultures were exposed to vitamin C (0-10 mM) for different time periods (0-2 h). Electron paramagnetic resonance spectroscopy revealed the intracellular formation of ascorbate free radical in a dose- and time-dependent fashion. Vitamin C also induced formation of intracellular reactive oxygen species in a dose-dependent fashion. It was observed that vitamin C induced morphological alterations and loss of cell viability in a dose- and time-dependent fashion, as measured by light microscopy and Alamar Blue redox cell viability assay, respectively. Vitamin C analogues failed to induce such changes. Vitamin C depleted cellular GSH levels in a dose-dependent fashion, suggesting that vitamin C altered thiol-redox status in BLMVECs. Antioxidants, intracellular iron chelator, and catalase protected cells against vitamin C-induced loss of redox-dependent cell viability, confirming the role of hydrogen peroxide and iron during redox cycling of vitamin C. These results, for the first time in detail, established that vitamin C at pharmacological doses induced oxidative stress and loss of redox-dependent cell viability in microvascular ECs. 相似文献
50.
Expression of CD14 by Hepatocytes: Upregulation by Cytokines during Endotoxemia 总被引:12,自引:0,他引:12
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