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81.
Understanding diet and energy balance as risk factors for breast, colon,
and other cancers requires information on the contribution of each factor
and of interactions among factors to cancer risk. Rodent models for breast
cancer provide extensive data on effects of dietary fat and calories,
energy balance, body weight gain, and physical activity on tumor
development. Analyses of the combined data from many studies have shown
clearly that quality and quantity of dietary fat and energy balance
contribute independently to increased mammary gland tumorigenesis. These
findings were seen in female rats fed diets high in fat (35-40% of
calories) compared to rats fed control diets, with approximately 10% of
calories as fat (Fay and Freedman, 1997, Breast Cancer Res. Treat. 46,
215-223). The methods used permit comparison of experimental and
epidemiological data, and they may be useful in extrapolating between
species and developing public health recommendations. In addition to the
contributions of lifetime-diet composition, intake, energy balance, and
physical activity to cancer risk, there are questions about the timing and
duration of alterations in these factors and about the "dose-response"
characteristics of cancer risk to the factors. Endocrine mechanisms may be
significant in mammary gland tumor risk, but experimental and
epidemiological data indicate that cancers at other sites, such as colon
and liver, also are influenced by the factors listed. Other diet and
lifestyle factors that influence energy, or specifically fat, metabolism
may also affect risk for cancers that are promoted by increased intake of
fat and calories. Studies of separate and interactive effects of dietary
fat, black tea, weight gain, and mammary gland tumorigenesis (Rogers, et
al, 1998, Carcinogenesis 19, 1269-1273) have been analyzed. Using
adjustment of carcinogenesis endpoints for body weight, tumor burden, and
latency, they were found to be related to weight gain within treatment
groups in 2 of 3 experiments.
相似文献
82.
Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1 总被引:6,自引:7,他引:6
Roepman R; van Duijnhoven G; Rosenberg T; Pinckers AJ; Bleeker-Wagemakers LM; Bergen AA; Post J; Beck A; Reinhardt R; Ropers HH; Cremers FP; Berger W 《Human molecular genetics》1996,5(7):1035-1041
The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X-
linked RP (XLRP), has been mapped previously to a chromosome interval of
less than 1000 kbp between the DXS1110 marker and the OTC locus at
Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization
(YRH)', we have recently identified a small XLRP associated microdeletion
in this interval, as well as several putative exons including the 3' end of
a gene that was truncated by the deletion. cDNA library screening and
sequencing of a cosmid centromeric to the deletion has now enabled us to
identify numerous additional exons and to detect several point mutations in
patients with XLRP. The predicted gene product shows homology to RCC1, the
guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our
findings suggest that we have cloned the long-sought RP3 gene, and that it
may encode the GEF of a retina-specific GTP-binding protein.
相似文献
83.
High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes 总被引:5,自引:0,他引:5
Shuber AP; Michalowsky LA; Nass GS; Skoletsky J; Hire LM; Kotsopoulos SK; Phipps MF; Barberio DM; Klinger KW 《Human molecular genetics》1997,6(3):337-347
As more mutations are identified in genes of known sequence, there is a
crucial need in the areas of medical genetics and genome analysis for
rapid, accurate and cost-effective methods of mutation detection. We have
developed a multiplex allele-specific diagnostic assay (MASDA) for analysis
of large numbers of samples (> 500) simultaneously for a large number of
known mutations (> 100) in a single assay. MASDA utilizes
oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA
samples are immobilized on a solid support and a single hybridization is
performed with a pool of allele-specific oligonucleotide (ASO) probes. Any
probes complementary to specific mutations present in a given sample are in
effect affinity purified from the pool by the target DNA. Sequence-specific
band patterns (fingerprints), generated by chemical or enzymatic sequencing
of the bound ASO(s), easily identify the specific mutation(s). Using this
design, in a single diagnostic assay, we tested samples for 66 cystic
fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell
anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations,
four mutations in Canavan disease, four mutations in Fanconi anemia, and
five mutations in BRCA1. Each mutation was correctly identified. Finally,
in a blinded study of 106 of these mutations in > 500 patients, all
mutations were properly identified. There were no false positives or false
negatives. The MASDA assay is capable of detecting point mutations as well
as small insertion or deletion mutations. This technology is amenable to
automation and is suitable for immediate utilization for high-throughput
genetic diagnostics in clinical and research laboratories.
相似文献
84.
Increase in the number of presynaptic large intramembrane particles during synaptic transmission at the Torpedo nerve-electroplaque junction 总被引:6,自引:0,他引:6
Small pieces of Torpedo electric organ were treated with 4-aminopyridine, a drug which greatly increases the duration of transmitter release in a single nerve impulse, transforming the normally brief electroplaque potential to a giant discharge. Specimens of tissue were cryofixed by rapid freezing using liquid coolants at precise time intervals during transmission of a single giant discharge, and then examined by freeze fracture. In each experiment, we monitored the electrical response of one specimen during the freezing run to check the physiological responsiveness of the tissue and to determine the precise time of contact with the cryogenic liquid. The general appearance of nerve terminals after cryofixation was similar to that of terminals from chemically fixed and cryoprotected tissue. The major morphological change observed during the time course of the giant discharge was a marked increase in the density of intramembrane particles larger than 10 nm on both the protoplasmic and external faces of the presynaptic membrane. This change appeared in specimens frozen within the first few milliseconds after the stimulus, that is, at a time corresponding to the onset of the rising phase of the potential (3 ms). At the end of the giant discharge, the particle density returned to control values with the same time course as the potential trace. Pits of 20 nm or larger, probably due to vesicle-membrane interaction, were found in a small proportion of nerve terminals. Their occurrence increased only at 120-150 ms after the stimulus, that is, a long time after the beginning of the giant potential and of the change in intramembrane particles. The size distribution of particles was also determined in the membrane of synaptic vesicles exposed by cross fracture of terminal boutons; it was found to be similar to that of the unstimulated presynaptic membrane and it did not change during the giant discharge. Stimulation experiments were also carried out in a modified solution containing no added calcium, 20 mM magnesium and 4-aminopyridine. The propagation of impulses along the nerves to the electric organ was not inhibited in the modified solution but acetylcholine release was prevented and no increase in particle density was found on the presynaptic membrane. These and previous biochemical experiments on this tissue suggest that the release of the neuro-transmitter acetylcholine is associated with a transient occurrence of large intramembrane particles on the two fracture faces of the presynaptic membrane.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
85.
86.
María Clara Restrepo-Méndez Aluísio JD Barros Kerry LM Wong Hope L Johnson George Pariyo Giovanny VA Fran?a Fernando C Wehrmeister Cesar G Victora 《Bulletin of the World Health Organization》2016,94(11):794-805B
ObjectiveTo investigate disparities in full immunization coverage across and within 86 low- and middle-income countries.MethodsIn May 2015, using data from the most recent Demographic and Health Surveys and Multiple Indicator Cluster Surveys, we investigated inequalities in full immunization coverage – i.e. one dose of bacille Calmette-Guérin vaccine, one dose of measles vaccine, three doses of vaccine against diphtheria, pertussis and tetanus and three doses of polio vaccine – in 86 low- or middle-income countries. We then investigated temporal trends in the level and inequality of such coverage in eight of the countries.FindingsIn each of the World Health Organization’s regions, it appeared that about 56–69% of eligible children in the low- and middle-income countries had received full immunization. However, within each region, the mean recorded level of such coverage varied greatly. In the African Region, for example, it varied from 11.4% in Chad to 90.3% in Rwanda. We detected pro-rich inequality in such coverage in 45 of the 83 countries for which the relevant data were available and pro-urban inequality in 35 of the 86 study countries. Among the countries in which we investigated coverage trends, Madagascar and Mozambique appeared to have made the greatest progress in improving levels of full immunization coverage over the last two decades, particularly among the poorest quintiles of their populations.ConclusionMost low- and middle-income countries are affected by pro-rich and pro-urban inequalities in full immunization coverage that are not apparent when only national mean values of such coverage are reported. 相似文献
87.
The influence of gonadal steroids on the ultrastructure of glial cells and on the immunoreactivity for the specific astrocytic marker glial fibrillary acidic protein (GFAP) has been assessed in the neuroendocrine hypothalamus. The following parameters were analyzed in the arcuate nucleus of adult female rats: the number and the surface density of cells immunoreactive for GFAP, the number of glial profiles showing bundles of glial filaments, the size of the bundles of glial filaments, and the proportion of neuronal perikaryal membrane apposed by glial processes. These parameters were studied during the different phases of the estrous cycle, after ovariectomy, and after the administration of estradiol or progesterone to ovariectomized rats. No significant differences were detected in the number of GFAP-immunoreactive cells among the different experimental groups. The surface density of GFAP-immunoreactive material, the number of glial profiles in the neuropil, and the proportion of neuronal perikaryal membrane covered by glia were increased in the afternoon of proestrus and in the morning of estrus compared with other phases of the estrous cycle or to ovariectomized rats and showed a rapid (5 h) and reversible increase in ovariectomized rats injected with 17β estradiol, with a maximal effect by 24 h after the administration of the hormone. In contrast, the size of the bundles of glial filaments was decreased in the afternoon of proestrus, in the morning of estrus, and by the administration of estradiol to ovariectomized rats. The parameters studied were not affected by the administration of progesterone. However, progesterone (300 μg/rat) blocked the effects of 17β estradiol (1, 10, and 300 μg). The results suggest that glial cells may be actively involved in the modulation of neuroendocrine events by the hypothalamus. © 1994 Wiley-Liss, Inc. 相似文献
88.
Andres A; Morales JM; Praga M; Campo C; Lahera V; Garcia-Robles R; Rodicio JL; Ruilope LM 《Nephrology, dialysis, transplantation》1997,12(7):1437-1440
BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction
and to have an antinatriuretic effect. The existence of an interference of
cyclosporin with the vasodilating properties of endothelium mediated by
nitric oxide production could mediate these effects. On the other hand, the
infusion of the nitric oxide precursor L-arginine has been shown to induce
renal vasodilatation and to facilitate natriuresis in normal volunteers. We
have investigated the renal effects of the administration of an infusion of
L-arginine in renal transplant patients chronically treated with
cyclosporin. To facilitate the analysis of the data the effects of the
administration of a similar dose of cyclosporin on renal function during
the infusion of a vehicle were also investigated during the administration
of a vehicle of L-arginine. DESIGN: Ten male renal transplant patients,
chronically treated with cyclosporin and with a stable renal function were
studied during 2 consecutive days after the administration of the usual
morning dose of cyclosporin. The first day they received an intravenous
infusion of vehicle and the second the infusion of graded doses of
L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The
first day, after cyclosporin administration a significant fall (P <
0.01) was observed in natriuresis and kaliuresis in the absence of changes
in renal plasma flow and glomerular filtration rate. After the
administration of L-arginine significant (P < 0.01) increases of renal
plasma flow, glomerular filtration rate, and natriuresis were seen. The
increase in blood levels of cyclosporin after its administration did not
differ between days 1 and 2. CONCLUSION: These results indicate that
L-arginine facilitates renal vasodilatation and natriuresis in renal
transplant patients. Furthermore, the observed increase in sodium excretion
could indicate that L-arginine counteracts the antinatriuretic effect of
cyclosporin.
相似文献
89.
90.
L M Garcia-Segura 《Acta histochemica》1977,59(2):182-189
In this work is studied the tannin-iron method specificity when the ferrous chloride is replaced by other iron compounds. Nervous tissue and rat duodenum cuts are used. Cuts were treated with tannic acid and after with FeCl3; FeCl2; FeOHCl2; FeAc2; Fe2O3; FeSO4; NH4Fe(SO4)2 or colloidal iron solution. Dilution effect from every one of aforementioned iron compounds too is studied. The obtained results with those furnished by the OTA method by using the tannic acid in identical conditions are compared. Also several treatments of blockade were carried-out. The obtained results prove that iron ions play a different role in the mucins staining than in other demonstrable substances coloration in the nervous tissue. In the same way evidences that the iron ion that joins the mucins in the tannin-iron method is the FeOH++ ion were obtained. 相似文献