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21.
Localization of a gene for otosclerosis to chromosome 15q25-q26 总被引:5,自引:0,他引:5
Tomek MS; Brown MR; Mani SR; Ramesh A; Srisailapathy CR; Coucke P; Zbar RI; Bell AM; McGuirt WT; Fukushima K; Willems PJ; Van Camp G; Smith RJ 《Human molecular genetics》1998,7(2):285-290
Among white adults otosclerosis is the single most common cause of hearing
impairment. Although the genetics of this disease are controversial, the
majority of studies indicate autosomal dominant inheritance with reduced
penetrance. We studied a large multi- generational family in which
otosclerosis has been inherited in an autosomal dominant pattern. Five of16
affected persons have surgically confirmed otosclerosis; the remaining nine
have a conductive hearing loss but have not undergone corrective surgery.
To locate the disease- causing gene we completed genetic linkage analysis
using short tandem repeat polymorphisms (STRPs) distributed over the entire
genome. Multipoint linkage analysis showed that only one genomic region, on
chromosome 15q, generated a lod score >2.0. Additional STRPs were typed
in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and
D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis
gene.
相似文献
22.
The volume-activated chloride current in endothelial cells from bovine pulmonary artery is not modulated by phosphorylation 总被引:8,自引:0,他引:8
Géza Szücs Stephan Heinke Christine De Greef Luc Raeymaekers Jan Eggermont Guy Droogmans Bernd Nilius 《Pflügers Archiv : European journal of physiology》1996,431(4):540-548
We employed the patch-clamp technique to investigate the effects of various phosphorylation pathways on activation and modulation of volume-activated Cl- currents (I
Cl,vol) in cultured endothelial cells from bovine pulmonary arteries (CPAE cells). Half-maximal activation ofI
Cl,vol occurred at a hypotonicity of 27.5 ± 1.2%. Run-down of the current upon repetitive activation was less than 15% within 60 min. Stimulation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) or by (–)-indolactam did not affectI
Cl,vol. Down regulation of PKC activity by a 24-h preincubation of the cells with 0.2 mol/l PMA, or its inhibition by loading the cells with the specific inhibitory 19–31 pseudosubstrate peptide, did not influenceI
Cl,vol. Trifluoperazine and tamoxifen fully blockedI
cCl,vol with concentrations required for half-maximal inhibition of 3.0 and 2.4 mol/1 respectively. This inhibitory effect is probably not mediated by the calmodulin-antagonistic action of these compounds, because it occurs at free intracellular [Ca2+] of 50 nmol/l, which are below the threshold for calmodulin activation. The tyrosine kinase inhibitor herbimycin A (1 ol/1) and genistein (100 ol/1) did not affectI
Cl,vol Exposing CPAE cells to lysophosphatidic acid (1mol/1), an activator of p42 MAPkinase and the focal adhesion kinase p125FAK in endothelial cells, neither evoked a Cl– current nor affectedI
Cl,vol Neither wortmannin (10 mol/1), an inhibitor of MAP kinases and of PI-3 kinase, nor rapamycin (0.1 mmol/1), which interferes with the p70S6 kinase pathway, affectedI
Cl,vol Exposure of CPAE cells to heat or Na-arsenite, both activators of a recently discovered stress-activated tyrosine phosphorylation pathway, neither activated a current nor affected the hypotonic solution-induced Cl– current. We conclude that none of the studied phosphorylation pathways is essential for the activation of the Cl– current induced by hypotonicity. 相似文献
23.
24.
Ion channels and their functional role in vascular endothelium 总被引:41,自引:0,他引:41
Endothelial cells (EC) form a unique signal-transducing surface in the vascular system. The abundance of ion channels in the plasma membrane of these nonexcitable cells has raised questions about their functional role. This review presents evidence for the involvement of ion channels in endothelial cell functions controlled by intracellular Ca(2+) signals, such as the production and release of many vasoactive factors, e.g., nitric oxide and PGI(2). In addition, ion channels may be involved in the regulation of the traffic of macromolecules by endocytosis, transcytosis, the biosynthetic-secretory pathway, and exocytosis, e.g., tissue factor pathway inhibitor, von Willebrand factor, and tissue plasminogen activator. Ion channels are also involved in controlling intercellular permeability, EC proliferation, and angiogenesis. These functions are supported or triggered via ion channels, which either provide Ca(2+)-entry pathways or stabilize the driving force for Ca(2+) influx through these pathways. These Ca(2+)-entry pathways comprise agonist-activated nonselective Ca(2+)-permeable cation channels, cyclic nucleotide-activated nonselective cation channels, and store-operated Ca(2+) channels or capacitative Ca(2+) entry. At least some of these channels appear to be expressed by genes of the trp family. The driving force for Ca(2+) entry is mainly controlled by large-conductance Ca(2+)-dependent BK(Ca) channels (slo), inwardly rectifying K(+) channels (Kir2.1), and at least two types of Cl( -) channels, i.e., the Ca(2+)-activated Cl(-) channel and the housekeeping, volume-regulated anion channel (VRAC). In addition to their essential function in Ca(2+) signaling, VRAC channels are multifunctional, operate as a transport pathway for amino acids and organic osmolytes, and are possibly involved in endothelial cell proliferation and angiogenesis. Finally, we have also highlighted the role of ion channels as mechanosensors in EC. Plasmalemmal ion channels may signal rapid changes in hemodynamic forces, such as shear stress and biaxial tensile stress, but also changes in cell shape and cell volume to the cytoskeleton and the intracellular machinery for metabolite traffic and gene expression. 相似文献
25.
Shear stress induced membrane currents and calcium transients in human vascular endothelial cells 总被引:3,自引:0,他引:3
Gero Schwarz Guy Droogmans Bernd Nilius 《Pflügers Archiv : European journal of physiology》1992,421(4):394-396
We have measured membrane currents induced by shear stress together with intracellular calcium signals in endothelial cells from human umbilical cord veins. In the presence of extracellular calcium (Ca2+]o), shear stress induced an inward current at a holding potential of 0 mV which is accompanied by a rise in intracellular Ca2+ ([Ca2+]i). In the absence of extracellular calcium shear stress was unable to evoke a calcium signal but still induced a membrane current. The voltage dependence of the shear stress induced current was obtained from difference currents evoked by linear voltage ramps before and during application of shear stress. Its reversal potential Erev shifted from –2.3±0.8 mV (n=4) in a nominally Ca2+ free solution to +1.5±1.6 mV at 1.5 mM [Ca2+]o (n=4) and to +21.9±4.4 mV (n=7) at 10 mM [Ca2+]o. From our data we conclude that shear stress opens an ion channel that is 12.5±2.9 (n=7) times more permeable for calcium than for sodium or cesium. 相似文献
26.
A Srour AM El Tantawi N Khouja A Zouaoui J-P Lassau J Philippon Ph Cornu 《Surgical and radiologic anatomy : SRA》1994,16(1):117-119
Summary The anterior interhemispheric approach for aneurysms of the anterior communicating artery was studied in ten cadavers. This approach presents several advantages over the pterional approach widely used in neurosurgery. It allows direct access to the region of the anterior communicating artery complex with minimal retraction of the brain and preservatioin of the olfactory tract and the gyrus rectus.
Bases anatomiques de l'abord inter-hémisphérique antérieur lors de la chirurgie des anévrysmes de l'artère communicante antérieure
Résumé Ce travail concerne l'abord neurochirurgical des anévrysmes de l'artére communicante antérieure par voie frontale interhémisphérique. L'étude anatomique a été réalisée sur dix sujets. Cette exposition possède de nombreux avantages comparée à la voie ptérionale habituelle : voie d'abord reduite médiane permettant une visualisation directe et symétrique du complexe artériel de l'artére communicante antérieure ; avec le moindre manipulation et retraction du cerveau en respectant les voies olfactives et le gyrus rectus.相似文献
27.
The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation 总被引:5,自引:0,他引:5
Wetzels AM; Bastiaans BA; Hendriks JC; Goverde HJ; Punt-van der Zalm AP; Verbeet JG; Braat DD 《Human reproduction (Oxford, England)》1998,13(5):1325-1330
In a human in-vitro fertilization (IVF) programme, the effect of co-
culture of embryos with human fibroblasts was evaluated with respect to
pregnancy rate and embryo development. Patients were included in the study
after giving informed written consent. The IVF treatments were randomly
assigned by stratification of both age (<36 versus > or =36 years)
and previous IVF attempts (yes versus no). After fertilization was
established, the zygotes were transferred to a 4-well dish with or without
fibroblasts and cultured for 2 days. On the third day after ovum pick-up
(OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were
scored and a maximum of three embryos was transferred. Supernumerary
embryos of good quality were cryopreserved. The design of this study was a
group sequential trial with the objective of detecting differences between
pregnancy rates following IVF with conventional incubation or incubation in
co-culture with fibroblasts. This design included one evaluation at
half-way data collection. In the study, 148 patients had an OPU, of whom 77
were allocated to the co-culture group. There was no statistically
significant difference in pregnancy rate, cell number and embryo quality
between the two groups. The ongoing pregnancy rate per embryo transfer was
27% in co-culture and 30% in the conventional culture group. The
implantation rates per transferred embryo were 17 and 18% respectively.
Using a multivariate logistic regression model for the probability of
ongoing pregnancies, the odds ratio of co-culture, adjusted for age and
previous IVF attempts, was not statistically significant. In conclusion,
co-culture with human fibroblasts does not contribute to an improvement of
embryo quality nor to a higher pregnancy rate after IVF in an unselected
group of patients.
相似文献
28.
29.
Anderson RA; Wallace AM; Kicman AT; Wu FC 《Human reproduction (Oxford, England)》1997,12(8):1657-1662
Administration of supraphysiological doses of testosterone to normal men
causes inhibition of spermatogenesis, but while most become azoospermic,
30-55% maintain a low rate of spermatogenesis. We have investigated whether
there are differences in endogenous androgen production, of testicular and
adrenal origin, which may be related to the degree of suppression of
spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m.
injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic,
while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a
specific testicular product, was reduced to <10% of pretreatment values,
with no differences between the groups. Similar results were obtained for
other markers of testicular steroidogenesis. Urinary and plasma adrenal
androgens were also reduced during TE treatment: a statistically
significant decrease in both (P < 0.001 and P < 0.05 respectively)
was seen in the azoospermic but not oligozoospermic responders. These
results suggest that testicular steroidogenesis is decreased to <10% by
the administration of supraphysiological doses of exogenous testosterone.
Differences in the degree of ongoing steroidogenesis in the testis do not
appear to account for incomplete suppression of spermatogenesis, thus
differences in androgen metabolism may underlie this heterogeneous
response. A small but significant reduction in secretion of adrenal
androgens was also detectable, the relevance of which is unclear.
相似文献
30.
Time course of hypo-osmotic swellings of human spermatozoa: evidence of ordered transition between swelling subtypes 总被引:2,自引:1,他引:2
Hossain AM; Rizk B; Barik S; Huff C; Thorneycroft IH 《Human reproduction (Oxford, England)》1998,13(6):1578-1583
The hypo-osmotic swelling test (HOST or HOS test) usually takes into
consideration the total HOS response value with no emphasis either on the
value of the response subtypes or the response evaluation time. This study
investigated the time course of HOS responses and analysed their
physiological relevance. Raw semen spermatozoa and Percoll washed
spermatozoa were used in the experiment. The morphological changes in the
sperm tail were monitored by incubating the spermatozoa in the hypo-
osmotic solution for 16 different time periods. The HOS reactive
spermatozoa and the type of HOS reaction (swelling subtypes) of the samples
subjected to different duration of treatment were identified under a phase
contrast microscope. Also the fate of individual spermatozoa in a
hypo-osmotic environment were monitored for 30 min. In spermatozoa exposed
to a hypo-osmotic solution, the motility lasted usually less than 2 min and
motility characteristics were uniquely different from that of the
spermatozoa under iso-osmotic conditions. The HOS response development was
permanent but the motility loss due to hypo-osmotic shock was reversible up
to 1 min of incubation. There was an indication of ordered transition among
the HOS swelling subtypes apparently initiating with subtype b destined to
c, d, e, f and g. Further, the subtypes a and g showed gradual decrease and
increase, respectively, while subtype b showed abrupt initial increase and
then gradual decrease. Transition from b to g could be direct or via one or
more than one subtypes. Ultrastructure based analysis indicated that HOS
response subtypes are the apparent reflection of the differences in the
cytoskeletal assembly of the sperm tail and thus may be identifying
different physiological variants in the sperm population. These results
indicate that shorter incubation is essential to document the kinetics of
various HOS responses but the conventional HOS test misses these important
HOS features because of lengthy incubation. Since the time course of
ordered transition of HOS responses will vary more than the total HOS
response in semen of different aetiologies, the importance of HOS response
subtypes and response evaluation time should be taken into consideration
when applying HOS test.
相似文献