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31.
32.
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
33.
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
34.
The effect of ovarian steroids on epithelial ciliary beat frequency in the human Fallopian tube 总被引:3,自引:3,他引:3
Mahmood T; Saridogan E; Smutna S; Habib AM; Djahanbakhch O 《Human reproduction (Oxford, England)》1998,13(11):2991-2994
Using a method that detects variations in light intensity we have studied
the effect of ovarian steroids on human Fallopian tube epithelial ciliary
beat frequency in vitro. We have found that baseline ciliary beat frequency
averages between 5-6 Hz. Cilia from ampullary segments of the Fallopian
tube beat significantly faster (5.4 Hz+/-0.2) than those from fimbrial
segments (4.8 Hz+/-0.2). There was no significant difference in baseline
ciliary beat frequency at any other anatomical site in the Fallopian tube.
Incubation with progesterone (10 micromol/l) suppresses human Fallopian
tube epithelial ciliary beat frequency by 40-50%. This inhibition was
observed at similar magnitudes in all Fallopian tubes studied irrespective
of anatomical site. Progesterone-induced reductions in ciliary beat
frequency were concentration dependent and prevented by the progesterone
receptor antagonist mifepristone (RU486). Oestradiol alone (10 micromol/l)
had no effect on ciliary beat frequency at any anatomical site in the
Fallopian tube but did prevent the reduction in ciliary beat frequency seen
with progesterone when tissues were incubated with these two steroids
together.
相似文献
35.
36.
37.
A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region 总被引:4,自引:0,他引:4
38.
39.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation 总被引:22,自引:1,他引:22
Marsh DJ; Coulon V; Lunetta KL; Rocca-Serra P; Dahia PL; Zheng Z; Liaw D; Caron S; Duboue B; Lin AY; Richardson AL; Bonnetblanc JM; Bressieux JM; Cabarrot-Moreau A; Chompret A; Demange L; Eeles RA; Yahanda AM; Fearon ER; Fricker JP; Gorlin RJ; Hodgson SV; Huson S; Lacombe D; Eng C 《Human molecular genetics》1998,7(3):507-515
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403
amino acid dual specificity phosphatase (protein tyrosine phosphatase;
PTPase), was shown recently to play a broad role in human malignancy.
Somatic PTEN deletions and mutations were observed in sporadic breast,
brain, prostate and kidney cancer cell lines and in several primary tumours
such as endometrial carcinomas, malignant melanoma and thyroid tumours. In
addition, PTEN was identified as the susceptibility gene for two hamartoma
syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or
Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD
families and seven BZS families was screened for germline PTEN mutations.
PTEN mutations were identified in 30 of 37 (81%) CD families, including
missense and nonsense point mutations, deletions, insertions, a
deletion/insertion and splice site mutations. These mutations were
scattered over the entire length of PTEN , with the exception of the first,
fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified
in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD
mutations identified in this exon. Seven of 30 (23%) were within the core
motif, the majority (five of seven) of which were missense mutations,
possibly pointing to the functional significance of this region. Germline
PTEN mutations were identified in four of seven (57%) BZS families studied.
Interestingly, none of these mutations was observed in the PTPase core
motif. It is also worthy of note that a single nonsense point mutation,
R233X, was observed in the germline DNA from two unrelated CD families and
one BZS family. Genotype-phenotype studies were not performed on this small
group of BZS families. However, genotype-phenotype analysis inthe group of
CD families revealed two possible associations worthy of follow-up in
independent analyses. The first was an association noted in the group of CD
families with breast disease. A correlation was observed between the
presence/absence of a PTEN mutation and the type of breast involvement
(unaffected versus benign versus malignant). Specifically and more
directly, an association was also observed between the presence of a PTEN
mutation and malignant breast disease. Secondly, there appeared to be an
interdependent association between mutations upstream and within the PTPase
core motif, the core motif containing the majority of missense mutations,
and the involvement of all major organ systems (central nervous system,
thyroid, breast, skin and gastrointestinal tract). However, these
observations would need to be confirmed by studying a larger number of CD
families.
相似文献
40.
Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment 总被引:4,自引:0,他引:4
The antenatal variant of Bartter's syndrome is an autosomal recessive
kidney disease characterized by polyhydramnios, premature delivery,
hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous,
having been linked recently to mutations in an ATP- sensitive, renal outer
medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl
co-transporter, NKCC2. We characterized four of the mutations reported in
three heterozygous ROMK variants of antenatal Bartter's and found that each
expressed a distinct phenotype in Sf9 cells. One mutation expressed normal
function and appears to be an allelic polymorphism. The other three
mutations produced channels with significantly reduced K+fluxes. However,
the mechanisms in each case were different and reflected abnormalities in
phosphorylation, proteolytic processing or protein trafficking. The
different mechanisms may be important in the design of appropriate therapy
for patients with this disease.
相似文献